Expressions of serum N-terminal osteocalcin and cytokeratin 5/6 in primary lung cancer patients with bone metastasis and their clinical significances / 肿瘤研究与临床

Objective:To explore the expressions of serum N-terminal osteocalcin (N-MID) and cytokeratin (CK) 5/6 in primary lung cancer patients with bone metastasis and their clinical significances.Methods:The clinical data of 96 patients with primary lung cancer admitted to Chengdu Second People's Hospital between February 2019 to February 2022 were retrospectively analyzed. All patients were divided into the bone metastasis group (38 cases) and the non-bone metastasis group (58 cases) according to whether bone metastasis occurred, and 45 healthy people who underwent physical examination during the same period were treated as the healthy control group. The expression levels of serum N-MID and CK5/6 in the bone metastasis group, the non-bone metastasis group and the healthy control group were compared. Logistic regression was used to analyze the factors affecting bone metastasis in patients with primary lung cancer; receiver operating characteristic (ROC) curve analysis was used to analyze the value of the expression levels of serum N-MID and CK5/6 in predicting bone metastasis in patients with primary lung cancer.Results:The composition ratio of patients with pathological stage Ⅲ-Ⅳ, serum bone-derived alkaline phosphatase and N-MID expression levels in the bone metastasis group were higher than those in the non-bone metastasis group (all P < 0.05). The expression level of serum N-MID in the bone metastasis group and non-bone metastasis group was higher than that in the healthy control group [(26.0±5.3) ng/ml, (15.3±3.1) ng/ml vs. (9.9±1.7) ng/ml, F = 224.27, P < 0.001], and there were statistically significant differences in the serum N-MID expression level of the pairwise comparison among the three groups (all P < 0.05). The expression level of serum CK5/6 in the bone metastasis group and the non-bone metastasis group was lower than that in the healthy control group [(3.6±0.7) ng/ml, (7.3±1.4) ng/ml vs. (10.6±2.4) ng/ml, F = 178.11, P < 0.001], and there were statistically significant differences in the serum CK5/6 expression level of the pairwise comparison among the three groups (all P < 0.05). Multivariate analysis showed that CK5/6, N-MID and bone-derived alkaline phosphatase were independent affecting factors for bone metastasis in patients with primary lung cancer ( OR = 4.088, 3.615, 2.892, all P < 0.05). ROC curve analysis showed that the optimal cut-off values of serum N-MID and CK5/6 expression levels for predicting bone metastasis in patients with primary lung cancer were 18.59 ng/ml and 4.71 ng/ml; the corresponding the area under the curve (AUC) was 0.881 and 0.862, respectively; and the specificity and AUC of the combination of serum N-MID and CK5/6 in predicting the bone metastasis in patients with primary lung cancer was 98.28% and 0.937 (95% CI 0.869-0.977), respectively; the AUC predicted by the combination of both was higher than that by serum N-MID or CK5/6 single (all P < 0.001). Conclusions:The expression levels of serum N-MID and CK5/6 in primary lung cancer patients with bone metastasis are abnormally changed. Clinical detection of serum N-MID and CK5/6 expression levels may be used as sensitive indicators for predicting the bone metastasis in patients with primary lung cancer.

Application values of progastrin-releasing peptide, neuron-specific enolase, cytokeratin 19 fragment antigen 21-1, squamous cell carcinoma antigen and human epididymis protein 4 in the diagnosis of lung cancer / 肿瘤研究与临床

Objective:To investigate the clinical values of progastrin-releasing peptide (Pro-GRP), neuron-specific enolase (NSE), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), squamous cell carcinoma antigen (SCCA) and human human epididymis protein 4 (HE4) detections in the diagnosis of lung cancer patients.Methods:The clinical data of 200 lung cancer patients who were admitted to the Second Affiliated Hospital of Xuzhou Medical University from January 2020 to December 2021 were retrospectively analyzed. According to the pathological type, the patients were divided into lung adenocarcinoma group (80 cases), lung squamous cell carcinoma group (75 cases) and small cell lung cancer group (45 cases). Fifty patients with benign lung diseases and 50 healthy physical examiners who were admitted to the hospital during the same period were selected. All the subjects were tested for the levels of Pro-GRP, NSE, CYFRA21-1, SCCA and HE4, and the differences of each index level in the subjects of different subgroups were compared. The receiver operating characteristic (ROC) curve was drawn, and using pathological diagnosis result as the gold standard, the diagnostic efficacy of each index alone and in combination for lung cancer was compared.Results:The serum levels of Pro-GRP, NSE, CYFRA21-1, SCCA and HE4 in lung cancer group were higher than those in the benign lung diseases group and the healthy control group (all P < 0.001). There were no statistical differences in the levels of serum Pro-GRP, NSE, CYFRA21-1, SCCA and HE4 between the benign lung diseases group and the healthy control group (all P > 0.05). The levels of Pro-GRP, NSE and HE4 in the small cell lung cancer group were higher than those in the lung adenocarcinoma group and the lung squamous cell carcinoma group (all P < 0.05). NSE and HE4 levels in the lung adenocarcinoma group were higher than those in the lung squamous carcinoma group (both P < 0.05), while CYFRA21-1 and SCCA levels were lower than those in the lung squamous carcinoma group (both P < 0.05). The AUC of lung cancer diagnosed by HE4 was the largest (0.813), the AUC of lung adenocarcinoma diagnosed by HE4 was the largest (0.824), the AUC of lung squamous carcinoma diagnosed by CYFRA21-1 was the largest (0.884), and the AUC of small cell lung cancer diagnosed by NSE was the largest (0.959). The AUC of lung cancer diagnosed by combined detection of 5 indicators was 0.951, the AUC of lung adenocarcinoma and small cell lung cancer diagnosed by combined detection of 5 indicators was 0.975 and 0.996, and the AUC of lung squamous cell carcinoma diagnosed by combined detection of CYFRA21-1, SCCA and HE4 was 0.967. Conclusions:The levels of Pro-GRP, NSE, CYFRA21-1, SCCA, HE4 and other indicators have certain clinical values in the diagnosis of lung cancer and its pathological types, and the combined detection of each index is more valuable than a single index.

Clinical significance of blood lipids, lipoproteins, PTX-3, TTF-1, NSE, and CYFRA21-1 levels in patients with advanced gastric cancer / 中国医师杂志

Objective:To investigate the significance of blood lipids [triglyceride (TG), total cholesterol (TC)], lipoproteins [high-density lipoprotein (HDL), low-density lipoprotein (LDL)], and serum levels of pentraxin-3 (PTX-3), thyroid transcription factor-1 (TTF-1), neuron specific enolase (NSE), and human cytokeratin 21-1 fragment (CYFRA21-1) in patients with advanced gastric cancer, and to provide a basis for the early, middle, and late diagnosis and treatment of gastric cancer.Methods:127 gastric cancer patients admitted to 3201 Hospital from January 2019 to January 2022 were selected as the research subjects. They were divided into early stage group ( n=45), mild stage group ( n=43), and late stage group ( n=39) based on their condition. Enzyme linked immunosorbent assay (ELISA) was used to detect blood lipids (TG, TC), PTX-3, TTF-1, NSE, CYFRA21-1, and chemical precipitation method was used to detect lipoprotein metabolism (HDL, LDL) in the three groups of patients. The differences in blood lipids, lipoproteins, PTX-3, TTF-1, NSE, and CYFRA21-1 between three groups of gastric cancer patients and the late stage group of gastric cancer patients before and after surgery were analyzed. Logistic regression analysis was conducted to investigate the correlation between blood lipids (TG, TC), lipoprotein (HDL, LDL), PTX-3, TTF-1, NSE, CYFRA21-1, and gastric cancer incidence. The predictive value of individual and combined detection of the above indicators for gastric cancer was analyzed using the receiver operating characteristic (ROC) curve analysis. Results:The results showed that the TG, TC, and LDL levels in the late stage group were higher than those in the mild stage and early stage groups (all P<0.05), while the HDL levels were lower than those in the mild stage and early stage groups (all P<0.05). The serum levels of PTX-3, TTF-1, NSE, and CYFRA21-1 were higher than those in the mild stage and early stage groups (all P<0.05). The postoperative levels of TG, PTX-3, TTF-1, NSE, CYFRA21-1, TC, and LDL in the late stage group were significantly lower than those before surgery (all P<0.05) and the HDL level was higher than that before surgery ( P<0.05). The levels of TG, TC, HDL, LDL, PTX-3, TTF-1, NSE, and CYFRA21-1 were correlated with the late onset of gastric cancer (all P<0.05). The ROC curve showed that the area under the ROC curve (AUC) of PTX-3, TTF-1, NSE, and CYFRA21-1 combined detection was significantly higher than that of PTX3, TTF1, NSE, and CYFRA211 alone. Among them, PTX-3+ TTF-1+ NSE+ CYFRA21-1 combined detection had the highest AUC, sensitivity, and specificity. Conclusions:Patients with advanced gastric cancer have abnormal levels of blood lipids (TG, TC), lipoprotein (HDL, LDL), and serum PTX-3, TTF-1, NSE, and CYFRA21-1. Effective intervention measures need to be developed based on the above indicators to improve survival rate.

The Role of Tumour Budding as a Prognostic Factor in Primary Invasive Ductal Carcinoma of Breast.

Background: Tumor budding is considered as an essential step in invasion and as a poor prognostic factor in carcinoma.It is used as the main prognostic factor in colon cancer but it is now gaining popularity in other tumor types. Objectives of the study was to determine tumor budding and categorize it into low grade and high grade in primary invasive breast cancer patients and to determine the association of tumor budding with clinicopathological characteristics. An attempt was also made to compare cytokeratin expression in intra- tumoral and budding sites. Method: It was an observational-analytical study including 50 cases of surgically resected modified radical mastectomy specimens diagnosed as invasive breast carcinoma in the tertiary care hospital from October 2018 to March 2020. Tumor buds were counted in H&E and IHC stained sections in 10 high power fields. IHC marker used was pan cytokeratin. Cases were classified into low tumor budding and high tumor budding. Correlation of tumor budding was done with all the established clinicopathological characteristics. Cytokeratin expression was compared in tumor proper and budding sites. Results: Among the 50 casesof invasive breast carcinoma, 24 cases showed high tumor budding (>4/10HPF) and 26 cases showed low tumor budding (?4/10HPF). High tumor budding was seen with larger size of the tumor, higher primary tumor staging, higher lymph node staging, presence of lymphovascular invasion, lymph node involvement and presence of necrosis with a significant correlation. Also cytokeratin expression was similar in tumor proper and budding sites in 92% of the cases. Interpretation & Conclusion: Tumor budding showed significant correlation with tumor size, primary tumor staging, lymph node staging, lymph node involvement, lymphovascular invasion and tumor necrosis. Thus it can be considered as a significant prognostic factor in the invasive breast carcinoma and can be incorporated in the reporting protocol for breast cancer.

Application value of magnetic resonance imaging targetoid enhancement combined with alpha-fetoprotein level in evaluating the expression of cytokeratin 19 in hepatocellular carcinoma / 中华消化外科杂志

Objective:To investigate the application value of preoperative clinical and magnetic resonance imaging (MRI) targetoid enhancement combined with alpha-fetoprotein in evaluating the expression of cytokeratin 19 (CK19) in patients undergoing radical resection for single hepatocellular carcinoma (HCC) without macrovascular invasion.Methods:The retrospective cohort study was conducted. The clinicopathological data of 220 patients who underwent radical resection for single HCC without macrovascular invasion in the General Hospital of Ningxia Medical University from January 2016 to December 2020 were collected. There were 171 males and 49 females, aged (56±11)years. Of the 220 patients, 52 cases showed positive CK19 expression, while 168 cases showed negative CK19 expression. Observation indicators: (1) MRI and immunohistochemical staining results of patients with different status of CK19 expression; (2) comparison of clinical features of patients with different status of CK19 expression; (3) comparison of MRI features in patients with different status of CK19 expression; (4) analysis of influencing factors for CK19 expression in patients and predictive value. The normality of continuous variables was tested using the Shapiro-Wilk test. Measurement data with normal distribution were expressed as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were expressed as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers and (or) percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was analyzed by the non-parameter rank sum test. The relevant clinical and imaging features with P<0.05 were included in the binary Logistic regression model. The receiver operating characteristic (ROC) curve was drawn and the area under curve (AUC) was used to evaluate the predictive efficiency of the model. Results:(1) MRI and immunohistochemical staining results of patients with different status of CK19 expre-ssion. Results of MRI examination in patients with positive CK19 expression showed the tumors with low-signal intensity on plain T1-weighted imaging, annular high enhancement in the arterial phase, clear boundaries in the portal venous phase, central enhance-ment in the delayed phase and targetoid high signals on diffusion-weighted imaging (DWI). Immuno-histochemical staining revealed a positive CK19 expression. Results of MRI examination in patients with negative CK19 expression showed the tumors with low-signal intensity on plain T1-weighted imaging, non-annular high enhancement in the arterial phase, unclear boundaries in the portal venous phase, low signals compared with peripheral liver tissue in the delayed phase and uniform high signals on DWI. Immunohistochemical staining revealed a negative CK19 expression. (2) Clinical features of patients with different status of CK19 expression. The neutrophil count and cases with alpha-fetoprotein (AFP) ≥400 μg/L were 3.07(2.21,4.41)×10 9/L and 26 in patients with positive CK19 expression, versus 2.72(2.05, 3.51)×10 9/L and 48 in patients with negative CK19 expression, showing significant differences between them ( Z=?2.06, χ2=8.17, P<0.05). (3) Compari-son of MRI features in patients with different status of CK19 expression. Cases with tumor diameter ≥ 5 cm and cases with tumor showing targetoid enhancement were 34 and 22 in patients with positive CK19 expression, versus 82 and 24 in patients with negative CK19 expression, showing significant differences between them ( χ2=4.38, 18.86, P<0.05). (4) Analysis of influencing factors for CK19 expression in patients and predictive value. Results of multivariate analysis showed that AFP ≥ 400 μg/L and targetoid enhance-ment were independent risk factors for positive CK19 expression in HCC patients [ odds ratio=2.09, 3.23, 95% confidence interval ( CI) as 1.06?4.13, 1.49?6.99, P<0.05]. Results of ROC curve analysis showed that the AUC of targetoid enhancement for predicting positive CK19 expression was 0.64 (95% CI as 0.57?0.71), with the sensitivity and specificity as 42.31% and 85.71%. The AUC of AFP ≥400 μg/L for predicting positive CK19 expression was 0.61 (95% CI as 0.53?0.68), with the sensitivity and specificity as 51.00% and 71.43%. The AUC of targetoid enhancement combined with AFP ≥400 μg/L for predicting positive CK19 expression was 0.69 (95% CI as 0.61?0.77), with the sensitivity and specificity as 67.31% and 63.10%, respectively. Conclusions:Targetoid enhancement and AFP ≥400 μg/L are independent risk factors for positive CK19 expression in patients with single HCC without macrovascular invasion. Their combination has clinical value for preoperative evaluation of CK19 expression.

Downregulation of cytokeratin 18 increases NMIIA expression and promotes breast cancer metastasis / 中国药理学通报

Aim To investigate the role of aberrant cytokeratin 18(CK18) expression in breast cancer metastasis, anrl to elucidate the mechanism by identif¬ying its target.Methods The expression of CK.18 in human breast cancer tissues and cells was determined using immunohistochemical staining and Western blot, respectively.CK18 expression in human breast cancer MCF-7 cells was effectively down-regulated by shRNA, and its effect on breast cancer metastasis was further determined by scratch wound healing assay.The co-lo- cation of CK18 and non-muscle II A ( NMIIA) in MCF-7 cells was examined using double immunofluo¬rescence staining.The effect of CK18 down-regulation on the levels of NMIIA and c-Abl-ERK signaling was quantified by Western blot.Results Lower CK18 lev¬els was found in metastatic than that in primary breast cancer tissues and in highly invasive MDA-MB-231 than that in MCF-7 cells.CK.18 down-regulation pro¬moted the wound repair ability of MCF-7 cells 72h after scratch.CK18 and NMIIA were shown to co-locate in cytoplasm of MCF-7 cells.Moreover, down-regulation of CK18 increased NMIIA expression and activated the c-Abl-ERK signaling pathway in MCF-7 cells.Con¬clusions Down-regulation of CK18 could promote me¬tastasis of breast cancer, which is related to increased NMIIA expression and the activation of c-Abl-ERK sig¬naling pathway.

Expressions of cytokeratin 14 and proliferating cell nuclear antigen in the Hertwig's epithelial root sheath of a Vps4b knockout mouse / 华西口腔医学杂志

OBJECTIVES@#The effect of Vps4b gene mutation on the expressions of cytokeratin 14 (CK14) and proliferating cell nuclear antigen (PCNA) in the Hertwig's epithelial root sheath (HERS) is investigated.@*METHODS@#The bilateral mandibular tissues of mouse on postnatal days 5, 9, 11, 15, and 19 were removed. The mandibular first molar tissue sections were obtained after paraffin embedding. The CK14 and PCNA expressions in the epithelial root sheath of the normal mouse and Vps4b knockout mouse were compared through immunohistochemistry.@*RESULTS@#On postnatal day 5, the normal mouse began to form HERS and had a strong positive PCNA expression in the HERS cells; on postnatal day 9, the HERS structure was continuous, and PCNA was positive in the HERS cells; on postnatal day 11, a small portion of HERS began to break, and PCNA was weakly positive in the HERS cells; on postnatal day 15, HERS continued to fracture; PCNA was weakly and positively expressed in the HERS cells on the root surface; on postnatal day 19, the tooth root reached normal physiological length, and PCNA was positively expressed in the HERS cells of the terminal part. Similar to the normal mouse, the gene knockout mouse also formed a HERS structure on postnatal day 5. However, HERS began to break on postnatal day 9. On postnatal day 19, only a few fragments of HERS were found on the root surface, and the root development was immature. Moreover, the expression intensity of PCNA in the gene knockout mouse was decreased.@*CONCLUSIONS@#The Vps4b gene mutation may change the CK14 and PCNA expressions, leading to abnormal root development.

Cytokeratin 13 promotes the radio-sensitivity of nasopharyngeal carcinoma HNE1 cells by inhibiting the PI3K/AKT/mTOR pathway via PTEN / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the effect of cytokeratin 13 (CK13) on radio-sensitivity of human nasopharyngeal carcinoma HNE1 cell line and its mechanism. Methods: HNE1 cells were divided into control group, anti-CK13#a group (CK13 knockdown), anti-CK13#b group (CK13 knockdown), control+sirolimus group (100 nmol/L sirolimus treatment for 1 h), and anti-CK13#a + sirolimus group (100 nmol/L sirolimus treatment for 1 h). After irradiation treatment (200 cGy/min irradiation for 5 min), cell proliferation in each group was measured by CCK-8 assay. Cell apoptosis rate in each group was determined by Flow cytometry. Expression of PI3K/AKT/mTOR signaling pathway related PTEN gene was detected by qPCR, and WB was used to detect the expressions of PI3K/AKT/mTOR signaling pathway related proteins. Results: In the case of radiotherapy, as compared with the control group, the proliferation of HNE1 cells after CK13 knockdown was significantly enhanced (P<0.01) while the apoptosis rate was significantly reduced (P<0.01), the contents of caspase-3 and γH2AX as well as the protein lever of PTEN in cells were significantly decreased, while the expressions of p-AKT and p-S6K were significantly increased (all P<0.01). Interestingly, additional treatment with sirolimus (PI3K/AKT/mTOR signaling pathway inhibitor) could rescue the accelerated cell proliferation and decreased cell apoptosis caused by CK13 knockdown (all P<0.05). Conclusion: CK13 knockdown can enhance the activity of PI3K/AKT/mTOR signaling pathway by down-regulating PTEN, and ultimately reduce the radio-sensitivity of nasopharyngeal carcinoma HNE1 cells.

Expresión Inmunohistoquímica: Citoqueratinas CK19, CK14, β-Catenina y Ki67 en el Ameloblastoma y Queratoquiste Odontogénico / Immunohistochemical expression: Cytokeratins CK19, CK14, β-Catenin and Ki67 in Ameloblastoma and Odontogenic Keratocyst / Expressão imunohistoquímica: Citoqueratinas CK19, CK14, β-Catenina e Ki67 no ameloblastoma e queratocisto odontogênico

Resumen Introducción y objetivo: Los tumores y quistes odontogénicos son lesiones que se presentan en los maxilares al derivarse del tejido odontogénico embrionario. El ameloblastoma es un tumor benigno de origen epitelial, intraóseo y extraóseo caracterizado por su expansión e invasión local. Por otro lado, el queratoquiste odontogénico es una lesión quística, intraósea, con un comportamiento agresivo localmente destructivo y altamente recurrente. Se estudio la expresión de las proteínas CK19, CK14, β-Catenina, Ki-67 en las biopsias procesadas de amaloblastomas y queratoquistes odontogénicos durante el 2015-2018 del Servicio de Patología Oral y Maxilofacial de la facultad de Odontología de la Universidad Nacional de Colombia. Materiales y métodos: Estudio de serie de casos donde se tomaron bloques de parafina con diagnóstico histopatológico ya confirmado ameloblastoma (9 bloques): CK19 / 14, Ki67, β-Catenina y queratoquiste odontogénico (16 bloques): CK19 / 14, Ki67. Resultados: El promedio de Ki67 en el ameloblastoma y el queratoquiste odontogénico fue del 32% y 22%, respectivamente. Para el ameloblastoma y el queratoquiste odontogénico la CK19 / 14 fueron positivo para todos los casos. Finalmente, la β-Catenina marcó intensamente positiva en todos los casos de ameloblastoma. Conclusiones: Estas lesiones pueden diagnosticarse usando hematoxilina eosina, apoyándose en marcadores inmunohistoquímicos para corroborar el diagnóstico o cuando desee determinar metástasis en lesiones malignas. La CK14 / 19 son marcadores odontogénicos que determinan el origen de la lesión, la β-Catenina determina el comportamiento agresivo de la patología y el Ki67 determina el comportamiento, pronóstico y el tratamiento de la patología presente.

Abstract Introduction and objective: Odontogenic tumors and cysts are lesions that occur in the jaws when derived from embryonic odontogenic tissue. Ameloblastoma is a benign tumor of epithelial origin, intraosseous, characterized by its expansion and local invasion. On the other hand, odontogenic keratocyst is a cystic, intraosseous and extraosseous lesion, with aggressive local destructive behavior and highly recurrent. to find the expression of the CK19, CK14, β-Catenin, Ki-67 proteins in the processed biopsies of odontogenic amaloblastomas and keratocysts during the 2015-2018 Department of Oral and Maxillofacial Pathology of the Faculty of Dentistry of the National University of Colombia. Materials and methods: Case series study where paraffin blocks were taken with histopathological diagnosis already confirmed ameloblastoma (9 blocks): CK19 / 14, Ki67, β-Catenin and odontogenic keratocyst (16 blocks): CK19 / 14, Ki67. Results: The average Ki67 in ameloblastoma and odontogenic keratocyst was 32% and 22%, respectively. For the ameloblastoma and the odontogenic keratocyst, CK19 / 14 was positive for all cases. Finally, β-Catenin marked intensely positive in all cases of ameloblastoma. Conclusions: These lesions can be diagnosed using only hematoxylin eosin, relying on immunohistochemical markers to corroborate the diagnosis or when you want to determine metastases in malignant lesions. The CK14 / 19 are odontogenic markers that determine the origin of the lesion, β-Catenin determines the aggressive behavior of the pathology and the Ki67 determines the behavior, prognosis and treatment of the present pathology.

Resumo Introdução e objetivo: Tumores e cistos odontogênicos são lesões que ocorrem nas mandíbulas quando derivadas de tecido odontogênico embrionário. O ameloblastoma é um tumor benigno de origem epitelial, intraóssea, caracterizado por sua expansão e invasão local. Por outro lado, o ceratocisto odontogênico é uma lesão cística intraóssea, com comportamento destrutivo local agressivo e altamente recorrente. Objetivo: encontrar a expressão das proteínas CK19, CK14, β-Catenin, Ki-67 nas biópsias processadas de amaloblastomas odontogênicos e queratocistos durante o Departamento de Patologia Oral e Maxilofacial 2015-2018 da Faculdade de Odontologia da Universidade Nacional de Colombia. Materiais e métodos: Estudo de séries de casos em que foram realizados bloqueios de parafina com diagnóstico histopatológico de ameloblastoma já confirmado (9 blocos): CK19 / 14, Ki67, β-catenina e queratocisto odontogênico (16 blocos): CK19 / 14, Ki67. Resultados: O Ki67 médio no ameloblastoma e no ceratocisto odontogênico foi de 32% e 22%, respectivamente. Para o ameloblastoma e o ceratocisto odontogênico, a CK19 / 14 foi positiva para todos os casos. Finalmente, a β-catenina marcou intensamente positiva em todos os casos de ameloblastoma. Conclusões: Essas lesões podem ser diagnosticadas usando apenas hematoxilina eosina, utilizando marcadores imunohistoquímicos para corroborar o diagnóstico ou quando você deseja determinar metástases em lesões malignas. Os CK14 / 19 são marcadores odontogênicos que determinam a origem da lesão, a β-catenina determina o comportamento agressivo da patologia e o Ki67 determina o comportamento, o prognóstico e o tratamento da patologia atual.

The prognostic role of thyroid transcription factor-1 in lung adenocarcinoma

Aims: In this study, we investigated the expression of thyroid transcription factor-1 (TTF-1) in lung adenocarcinoma patients' samples and analyzed the association of TTF-1 with clinicopathological parameters, prognosis, and treatment options in patients with lung adenocarcinoma. Subjects and Methods: This retrospective study enrolled 200 patients who were histologically confirmed lung adenocarcinoma with Stage I-IV disease, between 2008 and 2015 years. The cytological archive of these hospitals' Pathology Department was searched. The available slides and the clinical information were reviewed and correlated. All analyses were conducted by SPSS version 15.0 statistical software. Results: Sixty-five (32.5%) of the patients showed TTF-1 negativity and 135 (67.5%) of them showed TTF-1 positivity. The median survival for TTF-1 positive and negative patients was 19.6 and 12.2 months, respectively. We did not find any statistical significance in-between the parameters in terms of the survival data. In TTF-1-negative group, the survival time of epidermal growth factor receptor mutation positive (P = 0.049), cytokeratin 7 (CK7) positive (P = 0.009) patients and those who had received curative radiotherapy (P = 0.028) was significantly better as compared to TTF-1-positive group. We also analyzed the relation between TTF-1 and survival outcome or chemotherapy selection in Stage IV disease. We could not identify any correlation between TTF-1 and survival outcome or treatment selection. Conclusions: This study suggests that TTF-1 is not a favorable prognostic factor in lung adenocarcinoma patients. The prognostic role of CK7 and relationship between TFF-1 expression in lung adenocarcinoma and predictive role of TTF-1 expression for the selection of first-line treatment in Stage IV lung adenocarcinoma should be validated in prospective and randomized studies

Biochemical analysis of cytokeratin fragment 21-1 concentration and expression of cytokeratin 19 in oral potentially malignant disorders

Introduction: Cytokeratin fragment 21-1 (CYFRA21-1), a constituent of the intermediate filament protein is known to be elevated in cancer. In vitro cleavage of cytokeratin 19 (CK19) protein results in the release of it's fragments into the supernatants of premalignant cell lines. This study was designed with the aim to investigate the concentrations of CYFRA21-1 in serum and saliva of oral potentially malignant disorders (OPMD), to evaluate CK19 expression in tissues of the same patients and to correlate the levels of CYFRA21-1 concentration in serum and saliva with CK19 expression in OPMDs, and to compare it with oral squamous cell carcinoma (OSCC), which was taken as positive control. Materials and Methods: Concentration of CYFRA21-1 was measured in saliva and serum of 30 OPMD cases with five patients having OSCC using ELISA technique and analysis of CK19 protein expression in the tissue of same patients using immunohistochemical technique was done. Results: Concentration of CYFRA21-1 in saliva and serum with regard to CK19 protein expression in tissues was significantly higher in control group than in study groups. Conclusion: CYFRA21-1 can be used as a promising diagnostic molecule and as an adjunctive marker for early detection, disease staging, and monitoring

Induction chemotherapy for unresectable Stage III non-small-cell lung cancer may improve survival of induction chemotherapy responders as predicted by elevated levels of carcinoembryonic antigen and cytokeratin fragment 19 and classification as stage N3 cancer

Aims: The aim of this study is to investigate patients with unresectable Stage III non-small-cell lung cancer (NSCLC) receiving radiotherapy with induction and concurrent pemetrexed or docetaxel plus cisplatin (PP/DP) chemotherapy and to identify the subgroup most likely to benefit from induction chemotherapy (IC). Subjects and Methods: Patients with unresectable measurable Stage III NSCLC received two cycles of PP/DP IC followed by concurrent chemoradiotherapy at a dose of 60–66 Gy. Statistical Analysis Used: Cox regression analysis was performed to evaluate the prognostic factors for survival; logistic regression analysis was used to evaluate the predictors for response to IC, and the receiver operating characteristic curves were used to evaluate the independent factors predicting response. Results: Eighty patients were included; the median survival time (MST) was 22.1 months. Partial response (PR) to IC was an independent prognostic factor for overall survival. For patients in the PR and stable disease groups, the MST was 36.7 and 19.5 months, respectively. The independent predictors of PR to IC included classification as stage N3 cancer, baseline carcinoembryonic antigen (CEA) levels >10 ng/ml, and cytokeratin fragment 19 (CYFRA21-1) levels >6 ng/ml. With each additional independent predictor, the likelihood of having have PR to IC increased. Conclusions: Radiotherapy with induction and concurrent PP/DP chemotherapy is feasible for patients with unresectable Stage III NSCLC. IC may improve the survival of IC responders, as predicted by elevated CEA and CYFRA21-1 levels and classification as stage N3 cancer. Additional randomized trials on IC may consider these predictors to tailor individualized treatments

Immunohistochemistry of Canine Hair Follicle Stem Cells (cHFSCs) by using CK15 and CK19

Adult body harbors powerful reservoir of stem cells that maintains homeostasis by tissue regeneration and in response to disease and injury. Hair follicle is a dynamic mini organ supporting important biological functions of the body in maintaining homeostasis and skin tissue self-renewal. This study was carried out with the objective of finding the adult stem cells in canine hair follicular tissue. To conduct this study, adult canine skin samples (n=12) irrespective of breed and sex were collected. To characterize the hair follicle stem cells, paraffin sections of canine hair follicles were immunostained with positive hair follicle stem cell markers like Anti- cytokeratin 15 (CK15) and Anti-cytokeratin 19 (CK19) and FITC conjugated and HRP conjugated secondary antibodies were used. Immunoreactivities for CK15 and CK19 were observed in the bulge/isthmus region of hair follicles in between the infundibulum and suprabulbar regions and occupied most part of the peripheral layer of outer root sheath cell. Immunophenotyping of canine Hair Follicle Stem Cells (cHFSCs) in the bulge region of hair follicle helps in confirmation of in vitro culture of cHFSCs from the bulge region which will be further used for translational research

Differential diagnosis and unusual diffuse cytokeratin expression in renal paraganglioma: A case report

Paraganglioma is a rare neuroendocrine tumor arising from undifferentiated cells of the primitive neural crest. We report a case of renal paraganglioma in a 67-year-old patient. Computed tomography demonstrated a solid mass in the middle and lower pole of the right kidney. Sonography revealed an enlarged right kidney with an irregular shape but distinct border. Renal cell carcinoma was diagnosed provisionally; the tumor was completely resected and submitted for pathological examination. Unexpectedly, histopathology and immunohistochemistry confirmed paraganglioma arising from the renal parenchyma. In this study, we report the exceptional occurrence of Paired box gene 8 (PAX-8) expression in a renal paraganglioma. In addition, we demonstrated diffuse cytokeratin positivity in this renal paraganglioma. Although our report of a paraganglioma originating from the kidney is not unique, our finding expands the known immunophenotypic spectrum of this tumor. The awareness of the possible occurrence of cytokeratin diffuse positivity in paraganglioma is relevant to avoiding misdiagnosis of paraganglioma.

Diagnostic value of multi-slice spiral CT perfusion imaging combined with serum CYFRA21-1, CEA and NSE for peripheral non-small cell lung cancer / 解放军医学杂志

Objective To investigate the diagnostic value of multi-slice spiral CT (MSCT) perfusion imaging combined with serum cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA) and neuron specific enolase (NSE) for peripheral non-small cell lung cancer (NSCLC). Methods Based on diagnosis, 109 patients with suspected peripheral NSCLC admitted from Aug. 2017 to Aug. 2019 in the Xinxiang Central Hospital were divided into peripheral NSCLC group (n=65) and benign pulmonary nodule group (n=44). Another 56 healthy subjects undergone physical examination during the same period were selected as control group. The parameters of MSCT perfusion imaging and serum levels of CYFRA21-1, CEA and NSE in the 3 groups were compared. The receiver operating curve (ROC) was used to analyze the diagnostic value of MSCT perfusion imaging combined with serous levels of CYFRA21-1, CEA and NSE for peripheral NSCLC. Results The blood volume (BV) was larger in peripheral NSCLC group than those in benign pulmonary nodule group and control group [(10.76±1.26) ml/100 mg vs. (4.01±0.59) ml/100 mg and (2.32±0.42) ml/100 mg]; the same was for surface permeability (PS) [(42.56±5.60) ml/ (100 mg·min) vs. (16.13±1.88) ml/(100 mg·min) and (8.49±0.91) ml/(100 mg·min)]; and for the mean transit time (MTT) of contrast medium [(20.14±3.67) s vs. (12.85±1.49) s and (7.21±0.95) s]. All the BV, PS and contrast medium MTT were higher (larger) in benign pulmonary nodule group than those in control group (P<0.05). The serum level of CYFRA21-1 was higher in peripheral NSCLC group than that in benign pulmonary nodule group and control group [(8.94±1.67) ng/ml vs. (4.73±0.51) ng/ ml and (1.93±0.26) ng/ml]; the same was for the CEA level [(27.91±3.25) ng/ml vs. (7.88±0.92) ng/ml and (2.06±0.47) ng/ml]; and for the NSE level [(19.53±2.16) ng/ml vs. (15.02±1.74) ng/ml and (11.96±1.22) ng/ml]. All the serum levels of CYFRA21-1, CEA and NSE were higher in benign pulmonary nodule group than those in control group (P<0.05). The ROC results showed that the diagnosis of peripheral NSCLC alone and combined with MSCT perfusion imaging, serum levels of CYFRA21-1, CEA and NSE were 0.802, 0.794, 0.698, 0.712 and 0.841, respectively. The diagnostic value of combined detection of the four methods was higher than that of individual detection. Conclusion MSCT perfusion imaging combined with serum levels of CYFRA21-1, CEA and NSE have high diagnostic value for peripheral NSCLC.

A Rare Case of Sinonasal Ameloblastoma with Immunohistochemistry.

Introduction: Ameloblastoma is benign locally aggressivedentine epithelial tumor. Mandible and maxilla are commonsites of involvement. Calretinin is specific marker and usefulto differentiate ameloblastoma from Keratocystic odontogenictumor. The rarity of site and presentation of lesion makes usreport this case.Case report: 46 year old female had recurrent nasalblockage. Polyps in right nostrils were seen on Rhinoscopy.Polypectomy was done for suspected antrochoanal polyps.Ameloblastoma was diagnosed on histopathology andconfirmed by Immunohistochemistry with Cytokeratin,Calretinin and WT1.Conclusion: Preoperative diagnosis by biopsy in unilateralnasal masses should be carried out to expect the unexpected.Immunohistohemistry should be performed in cases havingrare site to confirm the diagnosis.

Usefulness of large-section cytokeratin 20 in the detection of intestinal wall infiltration and mesangial metastasis in patients with middle and lower rectal cancer

Objective: The objective of the study was to evaluate the usefulness of large-section cytokeratin 20 (CK20) staining technique in the detection of infiltration on the distal wall and mesangial metastasis in patients with middle and lower rectal cancer. Materials and Methods: A total of 62 patients with rectal cancer in the middle and lower segment were studied on large slices stained with CK20. Logistic regression was used to analyze the clinicopathologic factors related to distal low and middle rectal cancer metastasis to the mesorectum and rectal wall. Results: Two types of distal metastasis of the tumor were observed in the rectal wall in 18% (11/62) of the patients: submucosal invasion and muscularis propria invasion. The extent of distal metastasis to the rectal wall was around 0.5–1.0 cm. Four types of distal metastasis occurred in the mesorectum: lymph node invasion, blood and lymphatic vessel invasion, perineural invasion, and isolated neoplastic microfoci. Distal metastasis to the mesorectum was observed in 24% (15/62) of the patients. The extent of metastasis to the mesorectum was around 0.5–4.0 cm. Another three patients with microcapillary invasion in the distal mesorectum were observed by immunohistochemistry, as it was difficult to determine the spread by conventional hematoxylin and eosin staining. Conclusion: The large-section CK20 staining technique is useful for the detection of infiltration on the distal wall and mesangial metastasis in patients with middle and lower rectal cancer

Primary mucinous carcinoma of skin with a trichoadenomatous component: A rare case report

Primary mucinous carcinoma of the skin is a rare subtype of eccrine sweat gland tumors. Differentiating it from metastatic adenocarcinomas is important in the management of this condition. We report the case of a 55-year-old female presenting with a painless nodule, which was subsequently diagnosed as primary mucinous carcinoma of skin with a trichoadenomatous component. The possibility of a metastatic adenocarcinoma was ruled out by performing ultrasound abdomen, total body computed tomography, mammogram and colonoscopy.

Hair Follicle Nevus Located on the Neck: Comparison with Accessory Tragus, Cervical Chondrocutaneous Branchial Remnants and Trichofolliculoma

Hair follicle nevus (HFN) is a rare, benign, follicular hamartoma that most frequently presents as a congenital nodule on the face. We experienced a rare case of HFN on the neck of a 14-year-old boy and performed a pilot immunohistochemical study with cytokeratin 19 (CK19) to compare the staining pattern of hair follicles in HFN and its differential diagnoses, accessory tragus, cervical chondrocutaneous branchial remnants (CCBR) and trichofolliculoma. With hematoxylin and eosin stain, HFN showed numerous tiny hair follicles in the dermis with several sebaceous and eccrine glands, and perifollicular fibrous thickening. With CK19 stain, some hair follicles in HFN and CCBR showed positive expression, a few hair follicles in accessory tragus showed weak expression, and no hair follicles in trichofolliculoma showed expression. The present report supports the view that HFN, accessory tragus and CCBR are within the same spectrum of hamartomas.

A Report of Bone Marrow Metastasis of Colon Cancer as a Primary Diagnosis, Supported by Cytokeratin Immunohistochemical Staining

Bone marrow metastasis of colon cancer is rare. Here, we report a 56-year-old female patient who presented with pancytopenia. She was diagnosed with colon cancer accompanied by lung and axial skeleton metastasis. The bone marrow study showed metastatic carcinoma. Immunohistochemical (IHC) staining with anti-cytokeratin 7 (CK7) and anti-cytokeratin 20 (CK20) antibodies showed that the bone marrow samples were negative for CK7 and positive for CK20, consistent with metastatic colon cancer. To the best of our knowledge, there has been only one other reported case of bone marrow metastasis of colon cancer as the primary diagnosis in an adult patient in Korea. Bone and bone marrow metastases of colon cancer are regarded as uncommon. However, for proper management, bone marrows should be promptly examined in patients with solid tumors when unexplained cytopenia is noted, even if the origin of the tumor is known to be rarely metastatic to bone marrow. In addition, the use of cytokeratin IHC staining is helpful for determining the origin of metastatic carcinoma.