Cervical Intraepithelial Neoplasia grade 2 biopsy: Do p16INK4a and Ki-67 biomarkers contribute to the decision to treat? A cross-sectional study

ABSTRACT BACKGROUND: Managing cervical intraepithelial neoplasia grade 2 (CIN2) is challenging, considering the CIN2 regression rate, perinatal risks associated with excisional procedures, and insufficient well-established risk factors to predict progression. OBJECTIVES: To determine the ability of p16INK4a and Ki-67 staining in biopsies diagnosed with CIN2 to identify patients with higher-grade lesions (CIN3 or carcinoma). DESIGN AND SETTING: Cross-sectional study conducted at a referral center for treating uterine cervical lesions. METHODS: In 79 women, we analyzed the correlation of p16INK4a and Ki-67 expression in CIN2 biopsies with the presence of a higher-grade lesions, as determined via histopathology in surgical specimens from treated women or via two colposcopies and two cytological tests during follow-up for untreated women with at least a 6-month interval. The expression of these two biomarkers was verified by at least two independent pathologists and quantified using digital algorithms. RESULTS: Thirteen (16.8%) women with CIN2 biopsy exhibited higher-grade lesions on the surgical excision specimen or during follow-up. p16INK4a expression positively and negatively predicted the presence of higher-grade lesions in 17.19% and 86.67% patients, respectively. Ki-67 expression positively and negatively predicted the presence of higher-grade lesions in 40% and 88.24% patients, respectively. CONCLUSIONS: Negative p16INK4a and Ki67 immunohistochemical staining can assure absence of a higher-grade lesion in more than 85% of patients with CIN2 biopsies and can be used to prevent overtreatment of these patients. Positive IHC staining for p16INK4a and Ki-67 did not predict CIN3 in patients with CIN2 biopsies.

Inmunolocalización de citoqueratina 14, 19 y Ki-67 en el epitelio de pacientes con agrandamiento gingival

R E S U M E N En pacientes con ortodoncia aparecen eventos patológicos no deseados como agrandamiento gingival inducido por tratamiento de ortodoncia (AGTO) o hipertrofia gingival. El objetivo del estudio es identificar la distribución inmunohistoquímica de citoqueratina CK-14, CK-19 y Ki-67 en epitelio gingival de pacientes con AGTO. Se seleccionaron I3 pacientes divididos en: grupo control (n=6), conformado por individuos periodontalmente sanos no portadores de aparatología ortodóntica y grupo test (n=7), integrado por pacientes con AGTO. Los marcadores CK-14, CK-19 y Ki-67 fueron identificados mediante inmunohistoquímica con anticuerpos monoclonales y observados en un microscopio óptico Leica DM 500. En los pacientes del grupo test el tejido epitelial se mostró hipertrófico con pérdida en la continuidad de la membrana basal. La CK-14 y CK-19 fue positiva en el epitelio de todos los sujetos evaluados, con una expresión positiva de alta intensidad en células de la lámina basal del grupo test. El promedio de células positivas para Ki-67 en el grupo test fue de 56%. En conclusión, la CK-14, CK-19 y Ki-67 son marcadores con elevada inmunoreactividad en tejido gingival de pacientes con AGTO portadores de ortodoncia.

During orthodontic treatment, unwanted pathological events such as gingival overgrowth induced by orthodontic treatment or gingival hypertrophy may appear The objective of this study is to identify immunohistochemical distribution of cytokeratin CK-14, CK-19 and Ki-67 in the gingival epithelium of patients with gingival overgrowth induced by orthodontic treatment. Thirteen patients were selected divided into: control group (n = 6), conformed of periodontally healthy individuals without orthodontic appliances and the test group (n = 7), conformed of patients with gingival overgrowth induced by orthodontic treatment. The biomarkers CK-14, CK-19 and Ki-67 were identified by immunohistochemistry with monoclonal antibodies and observed in a Leica DM 500 optical microscope. Hypertrophic epithelial tissue with loss of continuity of the basement membrane was found in the test group patients. CK-14 and CK-19 were positive in the epithelial tissue of all the subjects evaluated, with a high intensity positive expression in the cells of the basal lamina of the test group. The average number of cells positive for Ki-67 in test group was 56%. In conclusion, CK-14, CK-19 and Ki-67 are biomarkers with high immunoreactivity in the gingival tissue of patients with gingival overgrowth induced by orthodontic treatment.

Durante o tratamento ortodôntico, eventos patológicos indesejados como o crescimento gengival induzido pelo tratamento ortodôntico (CGTO) ou hipertrofia gengival podem aparecer: O objetivo deste estudo é identificar a distribuição imuno-histoquímica das citoqueratinas CK -14, CK-19 e Ki-67 no epitélio gengival de pacientes com CGTO. Foram selecionados 13 pacientes divididos em: grupo controle (n=6), conformado por indivíduos periodontalmente saudáveis sem aparelhos ortodônticos e o grupo teste (n=7), conformado por pacientes com CGTO. Os biomarcadores CK-14, CK-19 e Ki-67 foram identificados por imuno-histoquímica com anticorpos monoclonais e observados em microscópio óptico Leica DM 500. Tecido epitelial hipertrófico com perda de continuidade da membrana basal foi encontrado nos pacientes do grupo teste. CK-14 e CK-19 foram positivos no tecido epitelial de todos os sujeitos avaliados, com expressão positiva de alta intensidade nas células da lâmina basal do grupo teste. O número médio de células positivas para Ki-67 no grupo teste foi de 56%. Em conclusão, CK-14, CK-19 e Ki-67 são biomarcadores com alta imunorreatividade no tecido gengival de pacientes com CGTO.

Agrandamiento gingival asociado al tratamiento de ortodoncia: análisis histológico e inmunohistoquímico de dos casos clínicos

El agrandamiento gingival asociado al tratamiento de ortodoncia (AGTO) es el crecimiento no controlado de la encía. Aquí reportamos dos casos clínicos de pacientes masculinos sistèmicamente sanos con AGTO generalizado, con asociación a la biopelícula dental y sin esta. En ambos pacientes se identificó un tejido epitelial hiperplásico con abundantes células positivas para Ki-67 y tejido conectivo rico en fibras de colágeno distribuidas aleatoriamente. Futuros estudios serán útiles para dilucidar las diferencias fisiopatológicas del AGTO con relación con el biofilm dental y sin esta.

Orthodontic treatment-induce gingival overgrowth (OTGO) is uncontrolled growth of the gingiva. Here, we report two clinical cases of systemically healthy male patients with generalized GH undergoing orthodontic treatment, with and without association with dental biofilm. In both patients, hyperplastic epithelial tissue was identified with abundant Ki-67 positive cells and connective tissue rich in randomly distributed collagen fibers. Future studies will be useful to elucidate the pathophysiological differences of OTGO with and without relation to dental biofilm.

Investigation of the histopathological level of Ki-67, caspase-3 expressions of the effects of hesperidin on wound healing in the rat esophagus

Purpose: The effects of hesperidin application on the wound caused by esophageal burns were investigated in this study. Methods: Wistar albino rats were divided into three groups: Control group: only 1 mL of 0.09% NaCl was administered i.p. for 28 days; Burn group: An alkaline esophageal burn model was created with 0.2 mL of 25% NaOH orally by gavage­1 mL of 0.09% NaCl was administered i.p. for 28 days; Burn+Hesperidin group: 1 mL of 50 mL/kg of hesperidin was given i.p. for 28 days to rats after burn injury. Blood samples were collected for biochemical analysis. Esophagus samples were processed for histochemical staining and immunohistochemistry. Results: Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were significantly increased in Burn group. Glutathione (GSH) content and histological scores of epithelialization, collagen formation, neovascularization was decreased. After hesperidin treatment, these values were significantly improved in the Burn+Hesperidin group. In the Burn group, epithelial cells and muscular layers were degenerated. Hesperidin treatment restored these pathologies in Burn+Hesperidin group. Ki-67 and caspase-3 expressions were mainly negative in control group; however, the expression was increased in the Burn group. In the Burn+Hesperidin group, Ki-67 and caspase-3 immune activities were reduced. Conclusion: Hesperidin dosage and application methods can be developed as an alternative treatment for burn healing and treatment.

Variability in the Epithelial Expression of Ki67 and Polarization Characteristics of Collagen in Odontogenic Cysts and Tumours

ABSTRACT Objective: To assess the proliferation of epithelium (using the Ki67 index) and the polarization pattern of collagen in selected odontogenic cysts and tumours. In addition, an exploratory analysis of the effect of inflammation on the proliferation rate was done. Material and Methods: Following immunohistochemical staining, the labelling/proliferation index of Ki67 was calculated. The thickness and corresponding polarization colour of 100 juxta-epithelial picrosirius red-stained collagen fibers were assessed using linear micrometry with an eyepiece reticule under × 1000 magnification. Inflammation was graded subjectively as mild, moderate, and severe. Results: Overall Ki-67 expression was higher in the radicular cyst, Odontogenic Keratocyst, Ameloblastoma, while suprabasal Ki-67 positivity was maximum in Odontogenic Keratocyst. The stromal collagen fibers in Ameloblastoma showed predominantly green birefringence, whereas Odontogenic Keratocyst had orange birefringence. There was no significant association of inflammation with Ki-67 expression or birefringence patterns. Conclusion: The highest Ki67 expression in the radicular cyst, followed by Odontogenic Keratocyst and Ameloblastoma. Differences in the collagen maturation pattern were noted innately in five lesions studied and were further influenced by inflammatory changes. Epithelial proliferation and concomitant expression of thickness and maturity of the stromal collagen are innate features of the lesion further influenced by inflammation in various odontogenic cysts and tumours and may, in turn, guide the clinical behavior.

Efficacy of quantitative parameters of dual-layer spectral detector CT in preoperative prediction of Ki-67 expression in esophageal squamous cell carcinoma / 中华放射学杂志

Objective:To explore the efficacy of quantitative parameters of dual-layer spectral CT in preoperative prediction of Ki-67 expression in esophageal squamous cell carcinoma (ESCC).Methods:From December 2021 to December 2022, 64 patients with histopathologically diagnosed ESCC were retrospectively analyzed at Liaoning Cancer Hospital & Institute. The expression level of Ki-67 in ESCC tumor tissue was detected by the immunohistochemical method. The patients were divided into the Ki-67 high expression group (the Ki-67 expression index≥30%, 47 cases) and the Ki-67 low expression group (the Ki-67 expression index<30%, 17 cases). The quantitative parameters of spectral CT were measured, including traditional 120 kVp CT value, 40 keV CT value, iodine density (ID), normalized iodine density (NID), and Z-effective in arterial and venous phases. Independent sample t test was used to compare the differences in the parameters between the Ki-67 high and low expression groups. The receiver operating characteristic (ROC) curve was drawn to evaluate the efficacy of each parameter in predicting Ki-67 expression. DeLong test was used to compare the area under the curve (AUC). Results:The 120 kVp CT value, 40 keV CT value, ID, and Z-effective in the arterial phase and the 120 kVp CT value, 40 keV CT value, ID, NID, Z-effective in venous phase in the Ki-67 high expression group were all higher than those in the Ki-67 low expression group ( P<0.05). There was no statistically significant difference in arterial phase NID between the two groups ( t=1.85, P=0.070). NID in the venous phase had the highest AUC in predicting high expression of Ki-67 in ESCC (AUC=0.965, 95%CI 0.923-1.000). With a venous phase NID value of 0.28 as the diagnostic threshold, the sensitivity and specificity were 93.6% and 100%. There was no significant difference in AUC between venous phase NID and venous phase ID (AUC=0.926) and Z-effective (AUC=0.909) ( Z=-1.52, 1.81, P=0.128, 0.071), but there was a significant difference of AUC between venous phase NID and 120 kVp CT value (AUC=0.719) and 40 keV CT value (AUC=0.747) ( Z=3.41, 3.30, P=0.001, 0.001). There were statistical differences of AUC between venous phase NID and each parameter of arterial phase ( P<0.05). Conclusion:The three spectral CT parameters (ID, NID, and Z-effective) in the venous phase have high diagnostic efficacy in predicting ESCC Ki-67 expression.

Carcinoma mamario RH negativo en el Hospital Clínico Quirúrgico Docente Celestino Hernández Robau / Rh negative breast carcinoma at the Teaching Clinic Surgical Hospital Celestino Hernandez Robau

RESUMEN Introducción: El carcinoma mamario negativo a la expresión de receptores hormonales (RH negativo) incluye los subtipos moleculares Her-2/neu y triple negativo, asociados ambos a una mayor actividad biológica del tumor y un pronóstico desfavorable. Objetivo: Determinar la incidenciade los carcinomas triples negativos y Her-2/neu en carcinomas mamarios y su relación con variables clínico-patológicas de valor pronóstico. Métodos: Se realizó unestudio descriptivo, de corte transversal, en el Hospital Celestino Hernández, Villa Clara, entre enero de 2017 a junio de 2019. Se incluyeron 293 mujeres con diagnóstico de carcinoma de mama infiltrante, a cuyas biopsias se les realizó estudio inmunohistoquímico determinando la incidencia de los subtipos moleculares triple negativo y Her2/neu y su relación con otras variables de valor pronóstico. Resultados: En la serie se determinó la incidencia de los subtipos moleculares triples negativo y Her2/neu. En ambos subtipos moleculares, más de las dos terceras partes de las pacientes fueron mayores de 50 años, presentaron tallas tumorales mayor de 2 cm en el momento del diagnóstico y tuvieron histología ductal. Destaca además la relación de ambos subtipos moleculares con formas histológicas moderada y pobremente diferenciadas del carcinoma mamario. De igual forma, en ambos subtipos, el índice de proliferación determinado por Ki67 fue alto en más de las dos terceras partes de las pacientes estudiadas. Conclusiones: La edad posmenopáusica, el tipo histológico ductal, el grado histológico alto, el alto índice de Ki67 y la talla tumoral mayor de 2 cm se asocian con frecuencia a subtipos moleculares del carcinoma mamario negativos a receptores hormonales.

ABSTRACT Introduction: The breast carcinoma which is negative to the expression of hormonal receptors (negative RH) includes the molecular subtypes Her2/neu and triple negative, that are both associated to higher biological activity and a worse forecast. Objective: To determine the real incidence of the subtypes triple negative and Her2/neu in breast carcinoma and its correlation with prognostic value clinic-pathological variables. Methods: A descriptive, cross-sectional study was done in the Hospital Celestino Hernández, Villa Clara, from January 2017 to June 2019. It was included 293 women with diagnosis of infiltrating breast carcinoma, whose biopsies were studied by immunohistochemistry, determining the incidence of the molecular subtypes triple negative and overexpression of Her-2 and its correlation with others prognostic value variables. Results: In the series it was determined the incidence of the molecular subtypes triple negative and Her2/neu. In both molecular subtypes more two third of patients were older than 50 years old, had tumor size larger than 2 cm at the moment of diagnosis and had ductal histology. The correlation of the both molecular subtypes with moderately and poorly histological types of breast carcinoma stands out. In the same way the proliferation index determined by Ki67 was high in more two third of the studied patients. Conclusions: The post-menopausal age, the ductal histologic type, high histologic grade, high index of Ki67 and tumor size larger than 2 cm are often associated to molecular subtypes of breast carcinomas which are negative to the expression of hormonal receptors.

Chagas disease affects the human placental barrier's turnover dynamics during pregnancy

BACKGROUND Trypanosoma cruzi crosses the placental barrier and produces the congenital transmission of Chagas disease (CD). Structural alterations of the chorionic villi by this parasite have been described in vitro, but little is known about trophoblast turnover in placentas from women with CD. OBJECTIVE To analyze the proliferation and fusion processes in placentas from women with CD. METHODS Archived human term placenta paraffin-embedded blocks were used, from women with CD (CDP), and no pathology (NP). Immunohistochemistry tests were performed for Ki67 to calculate the proliferation index (PI) of cytotrophoblast (CTB) and Syncytin-1, a fusion marker of syncytiotrophoblast (STB). Hematoxylin/Eosin stained sections were employed to analyze STB percentages, STB detachment areas and syncytial knots quantity. Non parametric Student's t-tests were performed (p < 0.05). RESULTS Syncytial knots and STB detachment significantly increased in placental villi from the CDP group. STB percentage was significantly lower in the CDP group as well as the PI and Syncytin-1 expression significantly decreased in these placentas, compared with control (NP). CONCLUSION Dynamic of trophoblast turnover is altered in placentas from women with CD. These changes may lead into a gap in the placental barrier possibly allowing the parasite entry into the chorionic villi.

The prognostic importance of PD-L1, PTEN, PHH3, and KI-67 expressions in invasive breast carcinoma

SUMMARY OBJECTIVE: The aim of this study was to investigate the relationship of PD-L1, PTEN, PHH3, and Ki-67 immunohistochemical stain expressions with prognostic clinicopathological parameters in breast cancer. METHODS: Lumpectomy and mastectomy materials from 85 patients operated at the Department of Pathology, Bolu Abant Izzet Baysal University, Faculty of Medicine between 2014 and 2019 were retrospectively reviewed. PD-L1, PTEN, PHH3, and Ki-67 expressions were examined. Immunohistochemical staining results were compared with clinicopathological parameters and found to be associated with prognosis. RESULTS: A statistically significant correlation was found between PD-L1 and large tumor size, high histological grade, multifocality, and lymphovascular invasion. A statistically significant correlation was found between the loss of PTEN and large tumor size and histological grade. There was a statistically significant correlation between PHH3 and advanced age, large tumor size, and high histological grade. A statistically significant correlation was found between Ki-67 and large tumor size, high histological grade, and lymphovascular invasion. CONCLUSION: PD-L1, PTEN, PHH3, and Ki-67 are regarded as potential biomarkers that can be used to predict the prognosis of breast cancer and to develop targeted therapies.

EGFR mutation, expression of PD-L1/Ki-67 and their correlation with clinical features in elderly NSCLC patients / 中华检验医学杂志

Objective:To investigate the mutation of epidermal growth factor receptor (EGFR), the expression of programmed death ligand 1 (PD-L1), cell proliferation-associated antigen (Ki-67) in elderly patients with non-small cell lung cancer (NSCLC), and their correlation with clinical feature such as gender, histological type and TNM stage.Methods:The tissue samples of 340 elderly NSCLC patients with definite histopathological diagnosis were collected from January 2020 to December 2020 in Huadong Hospital Affiliated to Fudan University, including 195 males and 145 females, age between 68.9±6.0 years. Patients were grouped according to clinical features such as gender, histological type and TNM stage. The expression of EGFR mutation, PD-L1 and Ki-67 were detected by Super-ARMS and immunohistochemistry. The correlation between tnem and clinical features was statistically analyzed, and the correlation between EGFR mutation and PD-L1/Ki-67 expression was further analyzed separately.Results:In elderly NSCLC patients′ tissues, the positive rate of EGFR mutation was 48.53% (165/340). L858R and 19del mutations were the most common types, which were 56.36% (93/165), 30.30% (50/165) respectively. The mutation rate of EGFR was higher in women, lung adenocarcinoma, well-differentiated, and low-stage patients, which were 65.52% (95/145), 53.77% (164/305), 56.75% (143/252), 52.53% (135/257) respectively. In addition, the positive rate of PD-L1 expression was higher in elderly patients with non-adenocarcinoma lung cancer and poorly differentiated adenocarcinoma, which were 37.14% (13/35), 24.53% (13/53) respectively. The negative rate of PD-L1 expression was higher in elderly patients with NSCLC in stage Ⅰ+Ⅱ, no lymph node metastasis and weakly positive Ki-67, which were 89.11% (229/257), 87.63% (248/283), 94.71% (197/208) respectively. Correlation analysis showed that EGFR mutation was negatively correlated with the expression of PD-L1 and Ki-67 (PD-L1: r=-0.22, P<0.001; Ki-67: r=-0.32, P<0.001). Conclusion:There is a negatively correlation between EGFR mutation and the expression of PD-L1 and Ki-67 in elderly NSCLC, suggesting that the combined detection of EGFR mutation and PD-L1 expression could provide the basis for precise targeted therapy for elderly NSCLC patients.

The screening of patients with hepatocellular carcinoma suitable for TACE after radical resection based on microvascular invasion and Ki-67 expression / 中华肝胆外科杂志

Objective:To investigate the patients with hepatocellular carcinoma suitable for transcatheter arterial chemoembolization (TACE) after radical resection who were screened based on microvascular invasion (MVI) and Ki-67 expression.Methods:Of 400 patients with hepatocellular carcinoma who underwent radical resection in the Affiliated Hospital of Qingdao University from January 2013 to December 2019 were included and analyzed retrospectively, including 324 males and 76 females, aged (59.7±9.8) years, ranging from 32 to 87 years. According to whether they received adjuvant TACE treatment after operation, they were divided into simple operation group ( n=210) and TACE + operation group ( n=190). The recurrence in the first year after operation was followed up by outpatient reexamination. Univariate and multivariate Cox regression analysis were used to analyze the influencing factors of recurrence free survival after surgical resection. Subgroup analysis was performed according to Ki-67 and MVI to compare the recurrence free survival. Results:Multivariate Cox regression analysis showed that patients with proportion of Ki-67 positive cells ≥27.5% ( HR=2.073, 95% CI: 1.433-3.000, P<0.001) and MVI positive ( HR=2.339, 95% CI: 1.584-3.456, P<0.001) had increased risk of recurrence after radical resection. The 1-year cumulative recurrence free survival rate in the simple operation group was 70.0%, and there was no significant difference compared with 67.9% in the operation + TACE group( χ 2=0.08, P=0.774). Subgroup analysis: in the low expression of Ki-67 combined with negative MVI group ( n=128), the cumulative recurrence free survival rate of one year after operation in the simple operation group ( n=84) was 91.7%, which was significantly higher than 72.7% in the operation + TACE group ( n=44)( χ 2=8.22, P=0.004). There was no significant difference in the 1-year cumulative recurrence free survival rate between the simple operation group and the operation + TACE group (both P>0.05) in patients of Ki-67 high expression combined with MVI negative or Ki-67 low expression combined with MVI positive. In the Ki-67 high expression combined with MVI positive group ( n=107), the cumulative one-year recurrence free survival rate in the simple operation group ( n=62) was 40.3%, which was significantly lower than 60.0% in the operation + TACE group ( n=45)(χ 2=4.22, P=0.040). Conclusion:High expression of Ki-67 (≥27.5%) combined with positive MVI are the prediction factors for postoperative TACE treatment. Low expression Ki-67 (<27.5%) combined with negative MVI was contraindicated for postoperative TACE treatment.

Correlation of mucin1 and Ki67 expression with clinical pathological characteristics and prognosis of intrahepatic cholangiocarcinoma / 中华肝胆外科杂志

Objective:To analyze the expression of mucin 1 (MUC1) and Ki67 in intrahepatic cholangiocarcinoma (ICC), and to explore the correlations between the expression of MUC1 and Ki67 and the clinicopathological features and prognosis of ICC patients.Methods:Clinical data of 398 patients with ICC admitted to Henan Provincial People's Hospital from January 2013 to March 2020 were retrospectively analyzed. A total of 104 patients were included in this study, including 67 males and 37 females, aged (56.6±9.3) years. Immunohistochemistry was used to detect the expression of MUC1 and Ki67 in cancer tissues. Univariate and multivariate Cox regression analysis were used to study the prognostic factors of ICC patients.Results:The expression of MUC1 was low in 65 patients and high in 39 patients. Ki67 expression was low in 52 patients and high in 52 patients. High expression of MUC1 was correlated with lymph node metastasis ( P<0.05), while high expression of Ki67 was correlated with tumor nodes number, lymph node metastasis and vascular invasion (all P<0.05). Multivariate analysis showed that ICC patients with high MUC1 expression ( HR=2.321, 95% CI: 1.420-3.792, P<0.001) and high Ki67 expression ( HR=2.012, 95% CI: 1.247-3.247, P=0.004) showed a poor prognosis after hepatectomy. ICC patients with high MUC1 expression ( HR=1.664, 95% CI: 1.058-2.618, P=0.028) and high Ki67 expression ( HR=1.883, 95% CI: 1.168-3.035, P=0.009) had a poor prognosis after hepatectomy. Conclusion:High expression of MUC1 and Ki67 is correlated with tumor growth and metastasis. MUC1 and Ki67 are independent risk factors for prognosis of ICC patients after hepatectomy.

Diagnostic value of spiral CT arterial enhancement fraction in colorectal cancer staging / 肿瘤研究与临床

Objective:To explore the diagnostic value of spiral CT arterial enhancement fraction (AEF) in clinicopathological staging of colorectal cancer.Methods:The clinical data of 151 newly diagnosed colorectal cancer patients (colorectal cancer group) and 86 patients who underwent physical examination with no history of colorectal disease (the control group) admitted to Shanxi Province Cancer Hospital from September 2019 to May 2021 were retrospectively analyzed. All research subjects received whole abdominal spiral CT plain scan and three-phase enhanced scan, and the obtained images were transferred to the Siemens Syngo.via post-processing workstation for post-processing to obtain the AEF color map and its quantitative parameter AEF value. The correlation of AEF value with colorectal cancer stage and Ki-67 was analyzed, and its diagnostic performance for clinicopathological staging of colorectal cancer was evaluated by using receiver operating characteristic curve.Results:The AEF values ??of patients at stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ colorectal cancer were (72±9)%, (65±11)%, (60±12)%, and (52±10)%, respectively, and the difference was statistically significant ( F = 22.15, P < 0.001). The AEF values ??of the control group and the colorectal cancer group were (85±6)% and (62±12)%, respectively, and the difference in AEF value of both groups was statistically significant ( t = 18.66, P < 0.001). The clinicopathological stage of colorectal cancer was negatively correlated with AEF value ( r = -0.548, P < 0.05). Taking the control group as the standard, the area under the curve (AUC) of AEF value for the diagnosis of colorectal cancer stage Ⅰ, Ⅱ, Ⅲ and Ⅳ were 0.866 (the sensitivity was 62.50%, the specificity was 96.51%) and 0.928 (the sensitivity was 76.74%, the specificity was 98.84%), 0.981 (the sensitivity was 92.68%, the specificity was 91.86%) and 1.000 (the sensitivity was 100.00%, the specificity was 98.84%), and the difference in diagnostic efficiency was statistically significant ( P < 0.05). The AEF value of colorectal cancer was negatively correlated with Ki-67 ( r = -0.537, P < 0.05). The Ki-67 positive index of patients at stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ colorectal cancer was (55±12)%, (67±10)%, (73±12)%, and (79±11)%, respectively, and the difference was statistically significant ( F = 11.94, P < 0.001); the Ki-67 positive index of patients at stage Ⅳ was higher than those at stage Ⅰ+Ⅱ ( t = 3.45, P = 0.001); the clinicopathological stage of colorectal cancer was positively correlated with Ki-67 ( r = 0.393, P < 0.001). Conclusions:AEF quantitative color map and AEF value can reflect the characteristics of arterial and venous blood supply in colorectal cancer lesions. AEF value analysis before surgery is helpful for the clinicopathological staging of colorectal cancer.

Values of Ki-67 expression level and 4 molecular types for risk classification of prognosis in medulloblastoma / 肿瘤研究与临床

Objective:To investigate the values of Ki-67 expression level and 4 molecular types for risk classification of prognosis in patients with medulloblastoma (MB).Methods:A retrospective study of 92 MB patients who underwent surgery and were confirmed by postoperative pathology in the First Affiliated Hospital of Zhengzhou University from January 2009 to January 2018 was performed. The clinical data and survival data of the patients were collected and sorted out. The overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier method, and the log-rank test was performed. Risk stratification of prognosis of patients was performed according to the Ki-67 expression level combined with molecular typing, the low-risk group had Ki-67 positive index ≤50% and WNT or SHH subtype, the medium-risk group had Ki-67 positive index ≤50% and GROUP 3 or GROUP 4 subtype, or Ki-67 positive index >50% and WNT or SHH subtype), and the high-risk group had Ki-67 positive index >50% and GROUP 3 or GROUP 4 subtype. The differences in OS and PFS among different risk groups were compared. A multivariate Cox proportional hazards model was used to assess factors affecting the survival of patients.Results:There were 50 cases (54.3%) with Ki-67 positive index ≤50% and 42 cases (45.7%) with Ki-67 positive index >50%. The 5-year PFS rate and OS rate of patients with Ki-67 positive index ≤50% were 46.9% and 63.1%, and patients with Ki-67 positive index >50% were 28.5% and 32.0%, there were statistical differences in PFS and OS between the two groups ( P values were 0.020 and 0.028). There were 16 cases (17.4%) of WNT subtype, 14 cases (15.2%) of SHH subtype, 40 cases (43.5%) of GROUP 3 subtype and 22 cases (23.9%) of GROUP 4 subtype, their 5-year PFS rates were 78.0%, 76.0%, 19.2% and 19.9%, respectively, and their 5-year OS rates were 82.1%, 76.0%, 40.2% and 0, respectively. MB patients with GROUP 3 or GROUP 4 subtype had poorer PFS and OS than patients with WNT or SHH subtype ( P values were 0.003 and 0.039). Ki-67 expression level and molecular typing were combined to carry out risk classification of prognosis. There were 12 cases (13.0%) in the low-risk group, 56 cases (60.9%) in the medium-risk group, and 24 cases (26.1%) in the high-risk group . There were statistical differences in PFS and OS among MB patients in low-, medium- and high-risk groups (both P < 0.001). Multivariate Cox regression analysis showed that radiotherapy and risk classification of prognosis as medium risk and low risk were independent protective factors for PFS (radiotherapy vs. no radiotherapy: OR = 0.263, 95% CI 0.124-0.556, P < 0.001; medium-risk group vs. high-risk group: OR = 0.069, 95% CI 0.008-0.581, P = 0.014; low-risk group vs. high-risk group: OR = 0.260, 95% CI 0.131-0.514, P < 0.001); radiotherapy and risk classification of prognosis as low risk were independent protective factors for OS (radiotherapy vs. no radiotherapy: OR = 0.221, 95% CI 0.097-0.503, P < 0.001; low-risk group vs. high-risk group: OR = 0.328, 95% CI 0.150-0.717, P = 0.005). Conclusions:The expression level of Ki-67 and 4 molecular types are related to the prognosis of MB patients. The combination of the two can be used to classify the prognosis risk of MB patients, which has reference significance for the prediction of prognosis of patients and the selection of individualized treatment plans.

Analysis of the correlation of PELP1/MNAR expression with expressions of estrogen receptor, human epidermal growth factor receptor 2, Ki-67 and PIK3CA gene mutation in invasive breast cancer / 肿瘤研究与临床

Objective:To investigate the correlation of PELP1/MNAR expression with expressions of estrogen receptor (ER), Ki-67, human epidermal growth factor receptor 2 (HER2) and PIK3CA gene mutation.Methods:A total of 80 paraffin-embedded tissue specimens of primary invasive breast cancer patients in the Fifth People's Hospital of Datong in Shanxi Province from January 2008 to December 2018 were collected. The expression of PELP1/MNAR was examined by immunohistochemistry EliVision tow-step method. The polymerase chain reaction (PCR)-Sanger sequencing method was used to detect the mutation of PIK3CA gene. The expressions of PELP1/MNAR among patients with different expression status of ER, Ki-67, HER2 and with or without PIK3CA gene mutation were compared, and the correlations between each index and the expression of PELP1/MNAR were analyzed.Results:The high expression rates of PELP1/MNAR protein in patients with ER-positive [86.1% (31/36) vs. 59.1% (26/44)], Ki-67 high expression [100.0% (13/13) vs. 65.7% (44/67)], HER2-positive [81.0% (34/42) vs. 60.5% (23/38)] were high, and the differences were statistically significant (all P<0.05). There was no significant difference in the high expression rate of PELP1/MNAR protein between patients with mutant and wild-type PIK3CA [60.0% (12/20) vs. 75.0% (45/60), P = 0.199]. The expression of PELP1/MNAR was negatively correlated with the expression level of ER ( r = -0.195, P < 0.05), positively correlated with the expression level of Ki-67 ( r = 0.198, P < 0.05), positively correlated with the expression level of HER2 ( r = 0.225, P < 0.05), and negatively correlated with lymph node metastasis ( r = -0.269, P < 0.05). Conclusions:The expression of PELP1/MNAR in invasive breast cancer is negatively correlated with the expression level of ER, and positively correlated with the expression level of Ki-67 and HER2. There is no correlation between PELP1/MNAR expression and PIK3CA gene mutation, and the two may play their own role in the PI3K-AKT-mTOR regulatory pathway of breast cancer.

Could the intestinal epithelial alterations promoted by roux-en-y gastric bypass explain higher tendency for colonic diseases in bariatric patients? / As alterações epiteliais intestinais promovidas pelo bypass em y-de-roux podem explicar maior tendência a doenças colônicas em pacientes bariátricos?

ABSTRACT Background: Intestinal diversions have revolutionized the treatment of morbid obesity due to its viability and sustained response. However, experimental studies suggest, after these derivations, a higher risk of colon cancer. Aim: To analyze the histological and immunohistological changes that the jejunojejunal shunt can produce in the jejunum, ileum and ascending colon. Method: Twenty-four male Wistar rats were randomly divided into two groups, control (n=12) and experiment (n=12) and subdivided into groups of four. Nine weeks after the jejunojejunal shunt, segmental resection of the excluded jejunum, terminal ileum and ascending colon was performed. Histological analysis focused on the thickness of the mucosa, height of the villi, depth of the crypts and immunohistochemistry in the expression of Ki-67 and p53. Results: Significant differences were found between the experiment and control groups in relation to the thickness of the mucosa in the jejunum (p=0.011), in the ileum (p<0.001) and in the colon (p=0.027). There was also a significant difference in relation to the height of the villus in the ileum (p<0.001) and the depth of the crypts in the jejunum (p0.001). The results indicated that there is a significant difference between the groups regarding the expression of Ki-67 in the colon (p<0.001). No significant differences were found between the groups regarding the expression of Ki-67 in the jejunum and ileum. In the P53 evaluation, negative nuclear staining was found in all cases. Conclusion: The jejunojejunal deviation performed in the Roux-in-Y gastrojejunal bypass, predispose epithelial proliferative effects, causing an increase in the thickness of the mucosa, height of the villi and depth of the crypts of the jejunum, ileum and ascending colon.

RESUMO Racional: As derivações intestinais revolucionaram o tratamento da obesidade mórbida pela sua viabilidade e resposta sustentada. Porém, estudos experimentais sugerem, após estas derivações, risco maior de câncer de cólon. Objetivo: Analisar as alterações histológicas e imunoistológicas que a derivação jejunojejunal possa produzir no jejuno, íleo e cólon ascendente. Método: Foram utilizados 24 ratos Wistar machos randomicamente divididos em dois grupos, controle (n=12) e experimento (n=12) e subdivididos em grupos de quatro. Nove semanas após a derivação jejunojejunal procedeu-se a ressecção segmentar do jejuno excluso, íleo terminal e cólon ascendente. Análise histológica focou na espessura da mucosa, altura dos vilos, profundidade das criptas e a imunoistoquímica na expressão do Ki-67 e p53. Resultados: Foram encontradas diferenças significativas entre os grupos experimento e controle em relação à espessura da mucosa no jejuno (p=0,011), no íleo (p<0,001) e no cólon (p=0,027). Também houve diferença significativa em relação à altura dos vilos no íleo (p<0,001) e profundidade das criptas no jejuno (p<0,001). Os resultados indicaram que existe diferença significativa entre os grupos em relação à expressão do Ki-67 no cólon (p<0,001). Não foram encontradas diferenças significativas entre os grupos em relação à expressão do Ki-67 no jejuno e no íleo. Na avaliação do P53, foi encontrada coloração nuclear negativa em todos os casos. Conclusão: O desvio realizado na derivação gastrojejunal em Y-de-Roux, predispõem efeitos proliferativos epiteliais, causando aumento da espessura da mucosa, altura dos vilos e profundidade das criptas do jejuno, íleo e cólon ascendente.

Progesterone and estradiol receptors and Ki-67 in the superficial and deep infiltrating endometriosis / Receptores de progesterona e estradiol e Ki-67 no estroma e no epitélio de endometriose superficial e profunda

ABSTRACT Introduction: Endometriosis is a hormone-dependent disease characterized by ectopic presence of endometrial tissue responsive to ovarian steroids. Estrogen and progesterone are the main regulators of endometrial tissue, and the expression of receptors of these hormones in the ectopic tissue seems to be related to the pathophysiology of the disease. Ki-67 is a marker of tissue proliferation and an important marker of epithelial kinetics. Endometriosis can be classified as superficial, in the peritoneum, and deep, when it extends into ligaments and other organs. Objective: Our objective was to analyze the expression of estrogen and progesterone receptors and Ki-67, through immunohistochemistry, in different sites of endometriosis tissues (superficial peritoneal/ovarian endometriosis and deep infiltrating endometriosis). Casuistic and methods: We studied nine patients; five with superficial and four with deep endometriosis. Statistical correlation was performed with the Shapiro-Wilk test (significance level of 5%) and linear correlation analysis using Spearman's non-parametric test (significance of 1%). There was a correlation of Spearman between the estrogen receptor variable and Ki-67 in patients with superficial endometriosis. There was also a correlation between the variables estrogen receptor and progesterone receptor in patients with deep endometriosis. Results: Contrary to what was found for superficial endometriosis, there is linear increase of the variables, with a strong and positive correlation coefficient. This demonstrates that the variation of estrogen receptors can be explained in 99.1% by the same variation of progesterone receptors in deep endometriosis. Conclusion: It is possible to infer that other factors are involved in the response to hormonal variations for superficial and deep endometriosis.

RESUMEN Introducción: Endometriosis es una enfermedad dependiente de hormonas que se caracteriza por la presencia ectópica de tejido endometrial sensible a los esteroides del ovario. El estrógeno y la progesterona son los principales reguladores del tejido endometrial, y la expresión de receptores de esas hormonas en el tejido ectópico parece tener conexión con la fisiopatología de la enfermedad. El Ki-67 es un marcador de proliferación tisular y de la cinética epitelial. La endometriosis puede ser clasificada en superficial y profunda, alcanzando ligamentos y otros órganos. Objetivo: El objetivo de este estudio fue analizar la expresión de los receptores de estrógeno y progesterona y Ki-67, mediante inmunohistoquímica en endometriosis superficial peritoneal/ ovárica y endometriosis infiltrativa profunda. Casuística y métodos: Estudiamos nueve casos: cinco de endometriosis superficial y cuatro de endometriosis profunda. La correlación estadística fue realizada con el test de Shapiro-Wilk (nivel de significación del 5%), y el análisis de correlación linear, por la prueba no paramétrica de Spearman (nivel de significación del 1%). Hubo correlación de Spearman entre la variable receptor de estrógeno (RE) y Ki-67 en pacientes con endometriosis superficial, y entre las variables RE y receptor de progesterona (RP) en pacientes con endometriosis profunda. Resultados: Al contrario de lo que se ha encontrado para endometriosis superficial, hay aumento lineal de las variables, con coeficiente de correlación fuerte e positivo. Eso demuestra que la variación de los receptores para estrógeno puede ser explicada en el 99,1% por la misma variación de los RP en la endometriosis profunda. Conclusión: Es posible deducir que otros factores estén involucrados en las diferentes respuestas hormonales para endometriosis superficial y profunda.

RESUMO Introdução: Endometriose é doença hormônio-dependente caracterizada pela presença ectópica de tecido endometrial responsivo aos esteroides ovarianos. O estrogênio e a progesterona são os principais reguladores do tecido endometrial, e a expressão de receptores desses hormônios no tecido ectópico parece ter relação com a fisiopatologia da doença. O Ki-67 é um marcador de proliferação tecidual e importante sinalizador da cinética epitelial. A endometriose pode ser classificada em superficial e profunda, atingindo ligamentos e outros órgãos. Objetivo: O objetivo deste estudo foi analisar a expressão dos receptores de estrógeno e progesterona e Ki-67, por meio de imuno-histoquímica em endometriose superficial peritoneal/ovariana e endometriose infiltrativa profunda. Casuística e métodos: Estudamos nove casos, cinco de endometriose superficial e quatro de endometriose profunda. A correlação estatística foi efetuada com os testes de Shapiro-Wilk (nível de significância 5%) e a análise de correlação linear, pelo teste não paramétrico de Spearman (1% de significância). Houve correlação de Spearman entre a variável receptor de estrogênio (RE) e Ki-67 em pacientes com endometriose superficial e entre as variáveis RE e receptor de progesterona (RP) em pacientes com endometriose profunda. Resultados: Ao contrário do que foi encontrado para endometriose superficial, há o aumento linear das variáveis, com coeficiente de correlação forte e positivo. Isso demonstra que a variação dos receptores para estrogênio pode ser explicada em 99,1% pela mesma variação dos RP na endometriose profunda. Conclusão: É possível inferir que estejam envolvidos outros fatores nas diferentes respostas hormonais para endometriose superficial e profunda.

MRI features of breast invasive lobular carcinoma and correlation with Ki-67 index / 中国医学影像技术

Objective: To observe MRI features of breast invasive lobular carcinoma (ILC), and to analyze the relationship of functional MRI parameters and Ki-67 index. Methods: Data of 184 patients with breast cancer confirmed pathologically were retrospectively analyzed, including 52 cases of ILC (ILC group) and 132 cases of invasive ductal carcinoma (IDC). All patients received preoperative breast MRI. MRI morphological manifestations and functional parameters were compared between 2 groups, and the relationships of functional MRI parameters and Ki-67 index of ILC were analyzed. Results: Compared with those in IDC group, Ki-67 indexes in ILC group were lower (t=-3.50, P<0.01), while non-mass-like enhancement was more common (χ2=48.74, P<0.01), ADC and time to peak (TTP) value were both higher (t=2.48, 2.98, both P<0.05). Ki-67 index of ILC was negatively correlated with ADC value (r=-0.67, P<0.01) and positively correlated with early enhancement rate (r=0.52, P<0.01). Conclusion: MRI findings of breast ILC had certain characteristics, providing references for preoperative diagnosis of ILC and prognosis assessment.

Clinical value of P16 and Ki-67 expressions in cervical biopsy for predicting early cervical cancer in patients with high-risk HPV infection / 中国基层医药

Objective@#To explore the positive expressions of P16 and Ki-67 proteins in cervical biopsy lesions of patients with high-risk HPV infection and abnormal detection of liquid-based thin-layer cytology test(TCT), and the clinical value in predicting occurrence of early cervical cancer.@*Methods@#A total of 120 patients with high-risk HPV infection(16 and 18 subtypes positive) and abnormal TCT in the Traditional Chinese Medicine Hospital of Linhai from January 2016 to July 2017 were enrolled in the study.The colposcopy was used to get cervical biopsy lesions for pathological diagnosis, immunohistochemical staining was used to detect P16 and Ki-67 proteins.@*Results@#There were up to 66 patients with HPV-16 positive, 34 cases with HPV-18 positive, other 20 cases with 16 and 18 positive; 6 cases of atypical squamous epithelial cells(ASC), 46 cases of low-grade squamous intraepithelial lesions (LSIL), 60 cases of high-grade SIL(HSIL), other 8 cases of cervical squamous cell carcinoma(SCC) were diagnosed by TCT; 5 cases of inflammation, 105 cases of CIN and 10 cases of SCC by pathologically diagnosis.The positive rates of P16 and Ki-67 proteins were gradually increased in patients with inflammation, CIN and SCC[0(0/5), 36.2%(38/105), 70.0%(7/10), χ2=4.382, P=0.036; 0(0/5), 40.0%(42/105), 80.0%(8/10), χ2=5.945, P=0.015]. The patients with CIN were followed up for 21~36 months, median time 29.5 months.Twenty-six patients progressed to SCC, at the end of follow-up, the positive rates of P16 and Ki-67 proteins in patients with SCC were significantly higher than those in the CIN patients without progress[61.5%(16/26) vs.39.2%(31/79), χ2=3.934, P=0.047; 69.2%(18/26) vs.41.8%(33/79), χ2=5.905, P=0.015].@*Conclusion@#The positive expression rates of P16 and Ki-67 proteins in cervical biopsy tissues are significantly higher in patients with high-risk HPV infection and abnormal TCT, which in patients with pathologically diagnosis of SCC are higher than CIN patients, the same results in CIN patients with SCC progression than non-progressing patients, suggesting that P16 and Ki-67 proteins are of great value in predicting occurrence of early cervical cancer.

Clinical value of P16 and Ki-67 expressions in cervical biopsy for predicting early cervical cancer in patients with high-risk HPV infection / 中国基层医药

Objective To explore the positive expressions of P 16 and Ki -67 proteins in cervical biopsy lesions of patients with high-risk HPV infection and abnormal detection of liquid -based thin-layer cytology test (TCT),and the clinical value in predicting occurrence of early cervical cancer .Methods A total of 120 patients with high-risk HPV infection(16 and 18 subtypes positive) and abnormal TCT in the Traditional Chinese Medicine Hospital of Linhai from January 2016 to July 2017 were enrolled in the study.The colposcopy was used to get cervical biopsy lesions for pathological diagnosis ,immunohistochemical staining was used to detect P 16 and Ki-67 proteins. Results There were up to 66 patients with HPV-16 positive,34 cases with HPV-18 positive,other 20 cases with 16 and 18 positive;6 cases of atypical squamous epithelial cells (ASC),46 cases of low-grade squamous intraepithelial lesions (LSIL),60 cases of high-grade SIL(HSIL),other 8 cases of cervical squamous cell carcinoma (SCC) were diagnosed by TCT;5 cases of inflammation,105 cases of CIN and 10 cases of SCC by pathologically diagnosis.The positive rates of P16 and Ki-67 proteins were gradually increased in patients with inflammation ,CIN and SCC[0(0／5),36.2%(38／105),70.0%(7／10),χ2 ＝4.382,P＝0.036;0 (0／5),40.0%(42／105),80.0%(8／10),χ2 ＝5.945,P＝0.015].The patients with CIN were followed up for 21～36 months,median time 29.5 months.Twenty-six patients progressed to SCC ,at the end of follow-up,the positive rates of P16 and Ki-67 proteins in patients with SCC were significantly higher than those in the CIN patients without progress [61.5%(16／26) vs.39.2%(31／79), χ2 ＝3.934,P＝0.047;69.2%(18／26) vs.41.8%(33／79),χ2 ＝5.905,P＝0.015].Conclusion The positive expression rates of P16 and Ki-67 proteins in cervical biopsy tissues are significantly higher in patients with high -risk HPV infection and abnormal TCT ,which in patients with pathologically diagnosis of SCC are higher than CIN patients,the same results in CIN patients with SCC progression than non -progressing patients,suggesting that P16 and Ki-67 proteins are of great value in predicting occurrence of early cervical cancer .