Preoperative prediction of Ki-67 level in hepatocellular carcinoma based on radiomics signatures during Kupffer phase of Sonazoid contrast enhanced ultrasound / 中华超声影像学杂志

Objective:To evaluate the value of Sonazoid contrast enhanced ultrasound (CEUS) in preoperative prediction of proliferating cell nuclear antigen 67 (Ki-67) level of hepatocellular carcinoma (HCC) by establishing predictive model based on radiomics features of Kupffer phase.Methods:From October 2020 to August 2021, patients with histologically confirmed HCC lesion and who underwent Sonazoid CEUS examination 1 week before surgery were prospectively enrolled. The radiomics signatures were extracted from the whole tumor region on gray scale images and Kupffer phase images. Two predictive radiomics models were constructed using radiomic method. The predictive performance of 2 models was compared.Results:A total of 50 patients with histologically confirmed single HCC lesions were prospectively enrolled in this study. Among them, histological results revealed 24 HCC lesions with high level representation of Ki-67 (>20%) and 26 HCC lesions with low level representation of Ki-67 (≤20%). Two radiomics predictive models were established based on gray scale images and Kupffer phase images respectively. While compared with model based on B-mode ultrasound images, model based on Kupffer phase images showed significantly higher area under receiver operating characteristic curve (0.753 vs 0.535, P=0.017), accuracy (0.720 vs 0.580, P=0.023) and sensitivity (0.458 vs 0.250, P=0.043). Calibration plot indicated that Kupffer phase model showed better consistency with the actual Ki-67 level than gray scale model. Conclusions:The radiomics model based on Kupffer phase features of Sonazoid CEUS is a preoperative and noninvasive prediction the presentation level of Ki-67 in HCC lesions.

Role of Ki67 protein in colorectal cancer

Colorectal cancer has become one of the most frequent malignancy and the leading cause of death from cancer globally. Global Burden Cancer in 2013 had placed colorectal cancer in third place morbidity level and forth most lethal cancer globally. Understanding prognostic marker is essential to increase prognosis prediction in patients with colorectal cancer, especially in patient with the later stages. Several studies have reported the prognostic value of Ki67 expression in patient with colorectal cancer. Ki67 protein expression is associated with proliferative activation from intrinsic cell population in malignant tumor cells, where Ki67 can be used as a marker for tumor aggressivity. Expressions from protein Ki67 are associated with proliferative activities from intrinsic cell population in malignant tumor cells, where Ki67 can be used as marker from tumor cell’s aggressivity. Several diagnostic applications for pKi67 has already been explained, where Ki67 is significantly higher in malignancy compared to normal tissue. pKi67 is also increased along with the decrease of tissue differentiation, and it correlates with the presence of metastasis that can not be seen and tumor clinical phase. Prognostic value from Ki67 had been investigated in many studies with their potential as reliable marker in breasts, soft tissue, lungs, prostate, cervix, and central nervous system. Positive expression from Ki67 in colorectal cancer shows a better prognosis in patient who received surgical treatment and adjuvant radiochemotherapy, but not in a patient who received only a surgical treatment.

Use of different fixation times and application of two immunohistochemical methods for detection of KIT and Ki67 proteins in canine cutaneous mast cell tumors / Utilização de diferentes tempos de fixação e métodos imuno-histoquímicos na detecção das proteínas KIT e Ki67 em mastocitomas cutâneos caninos

Due to the high prevalence of mast cell tumors (MCTs) in the diagnostic routine, several factors, especially prognostic, have been sought to determine the biological behavior of these neoplasms. Immunohistochemistry (IHC) is one of the main tools utilized to biologically differentiate more aggressive tumors from less aggressive ones. However, some immunostainings are influenced by formalin fixation, interfering with the results. This is both a retrospective and prospective study of MCTs diagnosed in laboratory routine. A total of 25 samples, without knowledge about fixation time, were analyzed in the retrospective study, whereas 12 samples, with known fixation times, were assessed in the prospective study. Two histologic grading systems (Patnaik and Kiupel), special staining of toluidine blue, and IHC for KIT and Ki67 proteins were applied in both studies. Additionally, two amplification systems (biotinylated and non-biotinylated) for Ki67 protein and counting of the argyrophilic nucleolar organizing regions (AgNOR method) were tested in the prospective study. In the retrospective study, greater agreement between the evaluating pathologists was observed when the Kiupel system was used. IHC staining for KIT protein was effective in both studies, regardless of fixation time. IHC staining for Ki67 protein was highly sensitive to formaldehyde, and staining failure was observed in 56% of the cases in the retrospective study. In the prospective study, samples fixed for longer than 24 hours showed a reduction in the number of stained cells (altering the determination of the cell growth fraction) or showed absence of IHC staining in both amplification systems. The use of the AgNOR method to evaluate the rate of cell proliferation may be an alternative when the fixation time of the neoplasm is unknown or longer than 24 hours.(AU)

Devido a alta prevalência dos mastocitomas cutâneos caninos (MCCs) na rotina diagnóstica, vários fatores, especialmente fatores prognósticos, têm sido buscados para auxiliar na determinação do comportamento biológico desse neoplasma. A imuno-histoquímica é uma das principais ferramentas empregadas para diferenciar tumores biologicamente mais agressivos de tumores menos agressivos. Entretanto, algumas imunomarcações sofrem influência pela fixação em formol, interferindo nos resultados. Este estudo compreendeu avaliar através de uma etapa retrospectiva e uma etapa prospectiva casos de MCCs diagnosticados na rotina laboratorial. Um total de 25 amostras, sem conhecimento do tempo de fixação, foi analisado no estudo retrospectivo e 12 amostras, com tempos de fixação conhecidos, no estudo prospectivo. Foram aplicados nos dois estudos, dois sistemas de graduação histológica (Patnaik e Kiupel), a coloração especial de azul de toluidina e a imuno-histoquímica para as proteínas KIT e Ki67. Adicionalmente, no estudo prospectivo, foram testados dois sistemas de amplificação (biotinilado e não biotinilado) para a proteína Ki67 e a técnica de AgNOR (contagem das regiões organizadoras nucleolares argirofílicas). Na etapa retrospectiva, observou-se uma maior concordância entre os patologistas avaliadores quando o sistema Kiupel foi utilizado. A imunomarcação para KIT se manteve eficaz em ambos os estudos, independentemente do tempo de fixação. A imunomarcação para o Ki67 mostrou-se altamente sensível ao tempo de fixação em formol, sendo observada falha na imunomarcação em 56% dos casos do estudo retrospectivo. No estudo prospectivo, constatou-se que amostras fixadas por mais de 24 horas em formol apresentaram redução na quantidade de células imunomarcadas (alterando a determinação da fração de crescimento celular) ou apresentaram ausência de imunomarcação em ambos os sistemas de amplificação. A utilização do método AgNOR, para avaliar a taxa de proliferação celular, pode ser uma alternativa quando o tempo de fixação do neoplasma for desconhecido ou superior a 24 horas.(AU)

Analysis on correlations between ultrasound features and positive expressions of CerbB-2 and Ki-67 in patients with breast cancer / 吉林大学学报(医学版)

Objective; To explore the correlations between the ultrasound features and the expressions of the molecular biological indicator human epidermal growth factor receptor 2 (CerbB-2) and Ki-67 in the patients with breast cancer. Methods; The ultrasonographic characteristics and paraffin section materials of 107 patients with breast cancer confirmed by pathology were collected. The correlations between the ultrasonographic characteristics and the expressions of CerbB-2 and Ki-67 were analyzed. Results; The positive expression rates of CerbB-2 and Ki-67 in breast cancer tissue were 73.83% (79/107) and 81.21% (87/107), respectively; the expressions of CerbB-2 and Ki-67 were positively correlated (r= 0. 264, P=0. 001). There were obvious correlations between the edge, size, shape, orientation, hyper-echoic halo, rear echo attenuation, micro calcification, flow signal 2-3 grade of breast cancer and the expression of CerbB-2 (P1, hyper-echoic halo, rear echo attenuation, micro calcification, flow signal 2-3 grade of breast cancer and the expression of Ki-67 (P 1 (P= 0.002) were the independent prognostic factors of breast cancer. Conclusion: There are significant correlations between some ultrasound features of breast cancer and the positive expressions of CerbB-2 and Ki-67 in the breast cancer tissue.

Bartholin's gland adenoma in a Saanen goat / Adenoma de glândula de Bartholin em cabra da raça Saanen

ABSTRACT: Tumors affecting Bartholin's gland are considered rare in human medicine; there are few reports in the veterinary literature, with descriptions occurring only in cows. This article described the clinical and pathological findings associated with Bartholin's gland adenoma in a goat. Clinically, a 7-year-old pregnant Saanen goat presented bilateral enlargement of the vulva that did not regress spontaneously after parturition. Grossly, these vulvar masses were multilobulated, contained cystic areas from which oozed a whitish fluid. Histopathology revealed an adenoma characterized by the proliferation of irregularly shaped neoplastic epithelial cells that formed tubular to glandular-like structures. These neoplastic cells demonstrated moderate anisokaryosis and evident nucleoli. The intratumoral proliferation index (PI) was estimated by immunoreactivity with the protein ki-67. Further, the glandular-like structures produced a Periodic Acid-Schiff positive secretion. A diagnosis of Bartholin's gland adenoma was established due to the anatomic location of the neoplastic growths, the histopathological features, and the PI of the tumor.

RESUMO: Tumores que afetam a glândula de Bartholin são considerados raros em humanos e há poucos relatos na medicina veterinária, sendo descrito somente em vacas. Este artigo descreve os achados clínicos e patológicos associados ao adenoma na glândula de Bartholin em uma cabra. O animal da raça Saanen, com sete anos de idade e gestante apresentava aumento de volume bilateral na região da vulva, que não regrediu após o parto. Macroscopicamente, a massa era multilobulada, com presença de vários cistos preenchidos por uma secreção esbranquiçada. A histopatologia revelou um adenoma, caracterizado por proliferação de células epiteliais de formato irregular que formavam estruturas tubulares semelhantes à glândulas. Estas células neoplásicas apresentavam anisocariose moderada e nucléolos evidentes. O índice de proliferação celular intratumoral (PI) foi estimado por imunorreatividade à proteína ki-67. Além disso, a secreção produzida por essas estruturas do tipo glandular, foi positiva na coloração do Ácido Periódico-Schiff. O diagnóstico de adenoma da glândula de Bartholin foi estabelecido pela localização anatômica dos tumores neoplásicos, características histopatológicas e à PI do tumor.

CHOP expression and its correlation with proliferative/apoptotic ratio in colorectal adenoma-carcinoma sequence under same genetic background / 中国病理生理杂志

AIM:To investigate the expression of C/EBP homologous protein (CHOP) and its correlation with proliferative/apoptotic ratio (PAR) in colorectal adenoma-carcinoma sequence under the same genetic background .ME-THODS:Four kinds of tissue samples under the same genetic background from 23 patients, including normal colorectal tissue, adenoma with low-grade intraepithelial neoplasia , adenoma with high-grade intraepithelial neoplasia and colorectal adenocarcinoma samples , were collected .TUNEL method and Ki-67 immunohistochemistry were applied to determine the PAR.The expression of CHOP was detected by immunohistochemistry SABC method .RESULTS: ( 1 ) Under the same genetic background , the level of CHOP expression is significantly higher in colorectal adenocarcinoma than that in the ade -noma with high-grade intraepithelial neoplasia , the adenoma with low-grade intraepithelial neoplasia and the normal muco-sa.The level of CHOP expression was significantly higher in the adenoma with high -grade intraepithelial neoplasia than that in the adenoma with low-grade intraepithelial neoplasia and the normal mucosa .The level of CHOP expression was signifi-cantly higher in the adenoma with low-grade intraepithelial neoplasia than that in normal mucosa .(2) Under the same ge-netic background , PAR was significantly higher in the colorectal adenocarcinoma than that in the adenoma with high -grade intraepithelial neoplasia , the adenoma with low-grade intraepithelial neoplasia and the normal mucosa .PAR was significant-ly higher in the adenoma with high-grade intraepithelial neoplasia than that in the adenoma with low-grade intraepithelial neoplasia and the normal mucosa .PAR was significantly higher in the adenoma with low-grade intraepithelial neoplasia than that in the normal mucosa.(3) CHOP levels were positively correlated with PAR in the adenoma with low-grade intraepi-thelial neoplasia , adenoma with high-grade intraepithelial neoplasia and colorectal adenocarcinoma .CONCLUSION:CHOP expression and PAR continuously increased and positively correlated along the adenoma -carcinoma sequence , indica-ting that endoplasmic reticulum stress mediates the carcinogenesis of colorectal adenomas .

Evaluación por inmunohistoquímica de la expresión de hormonas hipofisiarias y del marcador de proliferación celular Ki-67 en tejido de adenomas causantes de acromegalia / Immunohistochemistry for pituitary hormones and Ki-67 in growth hormone producing pituitary adenomas

Background: Growth hormone (GH) producing adenomas, frequently express several hormones. This condition could confer them a higher proliferative capacity. Ki-67 is a nuclear protein antigen that is a marker for proliferative activity. Aim: To measure the immunohistochemical hormone expression in pituitary adenomas, excised from patients with acromegaly. To determine if the pluríhormonal condition of these adenomas is associated with a higher proliferative capacity, assessed through the expression of Ki-67. Material and methods: Forty one paraffin embedded surgical samples of pituitary adenomas from patients with acromegalia were studied. Immunohistochemistry for GH, prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), adrenocorticotropin (ACTH) and for the expression of Ki-67 was carried out. Results: All samples were positive for GH. Twenty seven had positive staining for PRL, 12 had positive staining for glycoproteic hormones and 11 for PRL and one or more glycoproteic hormones. Mean staining for Ki-67 was Z.6±3.3 percent. There were no differences in the expression of this marker between mono or pluríhormonal tumors. The expression was neither associated with extrasellar extensión. Conclusions: Half of GH producing pituitary adenomas are pluríhormonal. There are no differences in the expression of Ki-67 between mono and plurihormonal adenomas.

An Analysis of p53, bcl-2 and Ki-67 Expressions, and Apoptosis in Rectal Cancer: Their Correlation with the Tumor Response after Preoperative Radiochemotherapy

Background : Preoperative radiochemotherapy (RCT) has been administered for locally advanced rectal cancer to increase the therapeutic benefits, and to preserve the sphincter in low-lying tumors, however, tumor responses after RCT are variable. Methods : Apoptotic index (AI), and expressions of Ki-67, p53 and bcl-2 were analyzed in pretreatment biopsies from 69 patients with rectal cancer by immunohistochemistry. Tumor response was graded in surgically resected specimens by using a three-scale grading system: no response (NR), partial remission (PR) and complete remission (CR). Results : CR was identified in 19 cases (28%), PR in 24 cases (35%), and NR in 26 cases (38%) of 69 cases. p53 protein was expressed in 49 cases (71%), whereas bcl-2 was in 42 cases (61%). The pretreatment Ki-67 labeling index was 65.4+/-3.4%. The tumor response was not associated with any of these markers. Tumors with CR/PR showed a higher AI (0.84+/-.84%/0.66+/-.52%) than that of tumors with NR (0.58+/-0.54%). There was a significant correlation between tumor response and the histologic differentiation (p=0.008) or recurrence (p=0.039). Conclusions : The AI revealed a tendency to increase in tumors with CR/PR, while expressions of p53 and bcl-2, and Ki-67 labeling index had little direct association with tumor response.

Expression of c-erbB-2 and ki67 proteins in simple intestinal metaplasia,atypical intestinal metaplasia and gastric adenocarcinoma / 中国现代普通外科进展

Objective:To study the expressions of c-erbB-2 and ki67 proteins in simple intestinal metaplasia(SIM),atypical intestinal metaplasia(AIM) and gastric adenocarcinoma,and the relationships among them.Methods:The immunohistochemical EnVision method was used to determine the expressions of c-erbB-2 and ki67 in 27 cases of SIM,26 cases of AIM and 37 cases of gastric adenocarcinoma.Results:The positive rates of c-erbB-2 and ki67 in gastric adenocarcinoma were significantly higher than that in SIM(P0.05).Conclusion:The high expression of c-erbB-2 and ki67 in AIM and gastric adenocarcinoma suggested that AIM may play an important role in gastric adenocarcinoma.The AIM is one kind of precancerosis of gastric adenocarcinoma.

A Study for Mechanism of Biliary Ductal Injury in Patients with Anomalous Pancreaticobiliary Ductal Union: A Study for Mechanism of Biliary Injury in APBDU / 한국간담췌외과학회지

PURPOSE: It has been known that clinical features of anomalous pancreaticobiliary ductal union (APBDU) are thought to result from cholestasis and regurgitation of pancreatic juice. The purpose of our study is to clarify the relationship of clinicopathological factors and to get information on mechanism of biliary ductal injury in APBDU. METHODS: A total of 23 patients who underwent operation for APBDU from March 1995 to March 2003 were examined. The results of patients were analyzed for their relevance to the clinicopathological factors such as age, sex, age at onset, size of cyst, grade of inflammation, type of APBDU, level of pancreatic enzymes sampled from biliary ductal system, and Ki67 labeling index. RESULTS: Level of amylase in biliary ductal system was decreased with age, especially after 20 years. The grade of hyperplasia in gallbladder was increased with level of amylase in gallbladder. The grade of inflammation in gallbladder was increased with age, but inflammation of gallbladder decreased with the level of amylase in gallbladder, and the size of cyst was increased with grade of inflammation and age. CONCLUSION: Level of amylase in the bile of biliary ductal system was decreased with age, especially after 20 years, which suggests that reflux of pancreatic amylase is closely related with onset of symptom in adult with APBDU. As far as mechanism of biliary ductal injury in APBDU is concerned, inflammation of biliary ductal system is increased with age and size of cyst. And hyperplasia of gallbladder is increased with the degree of regurgitation of pancreatic juice.

Expression of Ki67 and P53 proteins in gingival tissue after wearing four kinds of temporary crowns / 实用口腔医学杂志

Objective:To study the expression of Ki67 and P53 proteins in gingival tissue after wearing four kinds of temporary crowns.Methods:The experiment animal model was established by temporary prosthesis on dogs' teeth using chemical-curing resin,thermal-curing resin,DMG-TEMP crown material and SWIFT composite resin respectively.The immunohistochemistry Envision method was used to measure the expression of Ki67 and P53 proteins in gingival tissue before tooth preparation,after tooth preparation,1-and 2-week,1 month after wearing the crowns.The teeth without any treatment were surved as control.HE stained gingival tissue slices were observed under microscope.Results:The expression of Ki67 and P53 proteins in gingival tissue increased 1 week after wearing the chemical-curing resin crowns or thermal-curing resin crowns(P0.05).No pathological change was observed in all the samples.Conclusion:Chemical-curing resin crowns and thermal-curing resin crowns may increase the expression of Ki67 and P53 proteins in gingival tissue,but DMG-TEMP crowns and SWIFT resin crowns do not.None of the four kinds of temporary crowns may cause abnormal proliferation of gingival epithelia.