scholarly journals Immunohistochemical Expression of Ki-67 and p53 in Surface Epithelial Ovarian Tumour

2021 ◽  
Vol 8 (18) ◽  
pp. 1241-1245
Author(s):  
Mahendra Singh ◽  
Lubna Khan ◽  
Ankita Kamthan
Keyword(s):  
Cost Effective ◽  
Ovarian Tumour ◽  
Malignant Potential ◽  
Serous Carcinoma ◽  
Nuclear Staining ◽  
High Grade ◽  
Ki 67 ◽  
P53 Expression ◽  
Medical College ◽  
Proliferative Marker

BACKGROUND Surface epithelial ovarian tumour (SEOT) develops from the outer surface of ovary. It accounts for more than 90 % of all the ovarian tumours. Most of the SEOT are benign. Few SEOT are of low malignant potential or high malignant potential. The purpose of this study was to assess the rate of expression of proliferative marker Ki-67 and staining pattern of p53 in various histological types of SEOT. METHODS It was a randomised type of study carried out in the Department of Pathology, GSVM Medical College, Kanpur, for 2 years. It included 100 random patients with surgically resected specimens of SEOT. Ki-67 immunohistochemistry (IHC) was performed on all malignant cases and few random benign cases; and the percentage of immunopositive cells in each case was expressed as Ki-67 labelling index (Ki-67 LI). p53 expression was interpreted as positive when cells showed diffuse and intense nuclear staining in malignant cases. RESULTS Out of 100 cases, 70 were benign and 30 were malignant. Cases comprised of serous and mucinous histological subtypes. In all malignant cases, Ki-67 expression was found to be positive (Ki-67 LI > 1 %). Highest Ki-67 LI of 52 % was associated with high grade serous cystadenocarcinoma. High grade serous carcinoma (HGSC) had higher p53 positivity. 88.8 % of HGSC were p53 positive. CONCLUSIONS Ki-67 is a cost-effective proliferative marker; therefore, its assessment can be included in routine histopathological report of SEOT for better understanding of the biologic behaviour and aggressiveness of the tumour. p53 expression was more common in HGSC and can help in discriminating between HGSC and lowgrade serous carcinoma (LGSC). KEYWORDS p53, Ki-67, Ovarian Tumour, Serous, Mucinous, SEOT

An Immunostaining Panel for Diagnosis of Malignancy in Mucinous Tumors of the Pancreas

2001 ◽  
Vol 125 (6) ◽  
pp. 765-769
Author(s):  
Jin Zhao ◽  
Sharon X. Liang ◽  
Lou Savas ◽  
Barbara F. Banner
Keyword(s):  
Chronic Pancreatitis ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Pancreatic Tissue ◽  
Malignant Potential ◽  
Ki 67 ◽  
P53 Expression ◽  
Normal Pancreatic Tissue ◽  
Cystic Tumors ◽  
Her 2

Abstract Background.—The diagnosis of malignancy in pancreatic mucinous cystic tumors depends on demonstrating invasion that may be focal and require extensive sectioning. Objective.—To explore markers that may indicate malignant potential in mucinous cystic tumors. Design.—Routinely processed sections from resected specimens of 12 normal pancreata, 14 pancreata with chronic pancreatitis, 9 mucinous cystic tumors, and 30 invasive adenocarcinomas were immunostained with antibodies to p53, HER-2/neu, epithelial growth factor receptor (EGFR), transforming growth factor α (TGF-α), and Ki-67. Results.—Expression of p53, HER-2/neu, and Ki-67 was significantly more frequent in mucinous tumors than in normal pancreatic tissue and chronic pancreatitis tissue (P = .0003 to .05). Strong expression (more than one third of cells positive) and strong intensity (2+ and 3+) of staining of p53 and EGFR were seen only in carcinomas. Coexpression of p53/HER-2/neu and EGFR/HER-2/neu and a frequency of Ki-67+ nuclei of greater than 5% of cells discriminated between mucinous tumors and normal pancreatic tissue and chronic pancreatitis tissue. p53 expression was significantly more frequent in carcinomas than in mucinous tumor (P = .0326). Coexpression of p53/EGFR discriminated between mucinous tumors and carcinomas; however, TGF-α was not discriminative. Conclusions.—The immunostaining panel of p53, HER-2/neu, Ki-67, and EGFR can be helpful in indicating malignant potential in mucinous tumors of pancreas in routine pathology practice.

Establishment of Patient-Derived Tumor Xenograft Models of High-Risk Endometrial Cancer

2018 ◽  
Vol 28 (9) ◽  
pp. 1812-1820 ◽  
Author(s):  
Menghan Zhu ◽  
Nan Jia ◽  
Yanyan Nie ◽  
Jun Chen ◽  
Yahui Jiang ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Tumor Xenograft ◽  
Serous Carcinoma ◽  
High Grade ◽  
Primary Tumors ◽  
P53 Expression ◽  
Subrenal Capsule

ObjectiveHigh-risk endometrial cancers (ECs), including high-grade EC, serous carcinoma (SC), clear cell carcinoma, and carcinosarcoma, account for 50% of deaths due to ECs. Therapies for these cancers are limited, and patient-derived tumor xenograft (PDTX) models are useful tools for preclinical drug evaluation, biomarker identification, and personalized medicine strategies. Here, we used and compared 2 methods to establish PDTX models.MethodsFresh tumor tissues collected from 18 primary high-risk EC patients (10 high-grade ECs, 6 SCs, 1 clear cell carcinoma, and 1 carcinosarcoma) were engrafted subcutaneously and in the subrenal capsule in NOD/SCID for establishment and Balb/c-nu/nu mice for expansion. Histology and cytokeratin, estrogen receptor, progesterone receptor, and P53 expression were evaluated to assess the similarity of primary tumors and different generations of PDTX tumors. Whole-exome sequencing (WES) and RNA sequencing were used in 2 high-grade EC models to verify whether the genetic mutation profiles and gene expression were similar between primary and PDTX tumors.ResultsThe total tumor engraftment rate was 77.8% (14/18) regardless of the engraft method. The tumor engraftment rate was increased in subrenal capsule models compared with subcutaneous models (62.5% vs 50%, P = 0.464). The time to tumor formation varied significantly from 2 to 11 weeks. After subrenal capsular grafting, grafted tumors could be successfully transplanted to subcutaneous sites. We observed good similarity between primary tumors and corresponding different passages of xenografts.ConclusionsThe combination of 2 engrafting methods increases the tumor engraftment rate. The high tumor engraftment rate ensures the establishment of a high-risk EC biobank, which is a powerful resource for performing preclinical drug-sensitivity tests and identifying biomarkers for response or resistance.

scholarly journals Evaluation of biomarkers p16ink4a/ki-67 in cervical cytology for diagnosis of cervical intraepithelial neoplasia

2016 ◽  
Author(s):  
P. K. Sathija ◽  
S. Rajaram ◽  
V. K. Arora ◽  
B. Gupta ◽  
N. Goel
Keyword(s):  
Diagnostic Accuracy ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
Cervical Cytology ◽  
Low Grade ◽  
Nuclear Staining ◽  
Care Hospital ◽  
High Grade ◽  
Ki 67 ◽  
Good Diagnostic Accuracy

Background: Novel biomarkers, P16INK4a/Ki-67 are disease specific and identify risk of progression to cervical cancer. Aim: To test the clinical utility of biomarkers p16INK4a/Ki-67 in cervical intraepithelial neoplasia. Methodology: Experimental study was conducted over an 18 month period at a tertiary care hospital. 3500 sexually active women between 30-55 years were screened by VIA/VILI, Pap test & HPV-DNA PCR. All screen positive women (n=280) underwent colposcopy and biopsy if required. At the time of colposcopy repeat cervical smear were taken for evaluation of p16INK4a/Ki-67. Immunocytochemistry for p16INK4A and Ki-67 was done by partitioning one slide into two parts for each biomarker. For p16INK4A positivity, nuclear +/- cytoplasmic scoring and intensity score was calculated and final score obtained. For Ki-67 staining was exclusively nuclear. Staining patterns were categorized as negative, intermediate or strongly positive. Results: 86 women with abnormal cytology were evaluated with p16INK4A/Ki-67 immunocytochemistry and 20.9% (n=18) and 18.6% (n=16) were positive for each biomarker. For ASCUS (n=42) and LSIL (n=23) smears, specificity and NPV were 100% with a likelihood ratio (LR+) of 27 and 25 respectively suggesting good diagnostic accuracy. The combined sensitivity and specificity of p16INK4a/Ki-67 in detecting CIN-2+ lesion was 76.9% and 95.8% respectively with LR+ of 18.72 in high grade smears. Conclusions: p16INK4A/Ki-67 evaluation in cervical cytology are valuable biomarkers in ruling out or detecting CIN2+ in ASCUS and LSIL smears. Unnecessary intervention in large number of low grade smears can be avoided by applying these biomarkers. In high grade smears detection rate of biomarkers p16INK4A/Ki-67 was high and had a good diagnostic accuracy.

Clinical outcome in patients with endometrial papillary serous and endometrioid carcinomas as related to WT-1, Pax-2, and p16 immunohistochemical expression profiles

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16547-e16547
Author(s):  
M. Rollins-Raval ◽  
R. Byler Dann ◽  
R. P. Edwards ◽  
M. Chivukula
Keyword(s):  
Clinical Outcome ◽  
Expression Profiles ◽  
Postoperative Radiotherapy ◽  
Tumor Biology ◽  
Clinical Information ◽  
Serous Carcinoma ◽  
Nuclear Staining ◽  
High Grade ◽  
Papillary Serous Carcinoma ◽  
Strong Nuclear Staining

e16547 Background: Endometrial papillary serous carcinoma (EPS) can be difficult to differentiate histologically from high grade endometrial endometrioid carcinoma (EE). Both of these tumors often present with solid growth pattern with few papillary features. Recurrences have been found to be more frequent in EPS than high grade EE. These differences were found despite the same preoperative and postoperative radiotherapy and chemotherapy, indicating more aggressive tumor biology. To date, there are no well defined immunophenotypic or molecular methods to differentiate these two tumors or their clinical behavior. Methods: Eleven cases of EE and twenty-three cases of EPS were retrieved from our departmental archives and stained using Pax-2, WT-1 and p16 antibodies. For all three antibodies, a strong nuclear staining is considered positive. The intensity and proportion of cells positive are noted. Seven cases from each group were further examined for their staging and clinical outcome in terms of recurrence, metastasis and treatment. Results: WT-1 is negative in 100% of EE cases. p16 is positive in 95% of EPS cases, and only 55% of EE cases. In addition, out of the seven EPS patients whose clinical information was obtained, the three EPS patients who had strong Pax-2 staining are still alive more than two years status post surgical intervention, while four other EPS patients are deceased. The three patients with the strongly staining PAX-2 EPS tumors all had varying tumor characteristics, recurrence and adjuvant therapies. This finding is now being evaluated in the additional cases. Conclusions: WT-1, Pax-2 and p16 are useful to differentiate high grade EE and EPS cases. Strong Pax-2 staining in three cases of EPS with better outcome is an interesting finding that deserves further investigation. No significant financial relationships to disclose.

Cardiophrenic Lymph Node Metastasis of Ovarian High-grade Serous Carcinoma Showing Wild-type p53 Immunostaining Pattern and Aberrant CD56 Expression

2021 ◽  
pp. 106689692110061
Author(s):  
Hee Jung Kwon ◽  
Mijung Oh ◽  
Joungho Han ◽  
Sang Yong Song ◽  
Hyun-Soo Kim
Keyword(s):  
Lymph Nodes ◽  
Splice Acceptor Site ◽  
Serous Carcinoma ◽  
Acceptor Site ◽  
Sequencing Analysis ◽  
High Grade ◽  
Wild Type ◽  
P53 Expression ◽  
Cd56 Expression ◽  
Wild Type P53

Patterns of p53 immunostaining are used as a surrogate marker for tumor protein 53 ( TP53) mutations in the diagnosis of ovarian high-grade serous carcinoma (HGSC). We present a rare case of ovarian HGSC that metastasized to the diaphragm and cardiophrenic lymph nodes and showed the immunostaining pattern of wild-type p53 and aberrant neural cell adhesion molecule (CD56) expression. A 63-year-old woman developed multifocal metastases in the diaphragmatic pleura and cardiophrenic lymph nodes. Because she had a history of ovarian HGSC and pulmonary adenocarcinoma, we considered the possibility that the metastatic carcinoma was of either ovarian or pulmonary origin. Immunostaining revealed that the tumor cells were negative for thyroid transcription factor 1 but positive for Wilms tumor 1. The tumor additionally exhibited strong membranous CD56 expression and patchy p53 expression, both of which were inconsistent with the characteristics of ovarian HGSC. However, targeted sequencing analysis revealed that the tumor harbored a pathogenic mutation at the splice acceptor site of TP53 intron 9 (c.994-1G>C).

Ki-67, p53, and clinical outcomes of patients with triple-negative breast cancer.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 142-142 ◽  
Author(s):  
Yasuyuki Nishiyama ◽  
Reiki Nishimura ◽  
Tomofumi Osako ◽  
Yasuhiro Okumura ◽  
Nobuyuki Arima
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Prognostic Significance ◽  
Significant Prognostic Factor ◽  
Nuclear Staining ◽  
Ki 67 ◽  
P53 Expression

142 Background: Triple-negative breast cancer (TNBC) tends to produce a poor prognosis because of aggressive tumor biology and lack of targeted agents. Breast cancer with a high Ki-67 value responds better to chemotherapy but is associated with lower relapse-free (RFS) and overall survival rates. The basal-like subtype overlaps with TNBC in approximately 70% to 80% of the cases, and the vast majority of basal-like subtypes have mutated p53. The aim of this study was to evaluate the clinical and prognostic significance of Ki-67 and p53 in patients with TNBC. Methods: We retrospectively reviewed 1,711 patients with pT1-3 invasive breast cancer diagnosed between 2001 and 2010. Of the 200 TNBC cases, 165 patients received adjuvant chemotherapy. Cases were classified as luminal (ER+ and/or PR+ and HER2-), HER2 disease (HER2+) and TNBC (ER-, PR- and HER2-) subtypes. Estrogen receptor (ER) and progesterone receptor (PR) positivity was defined as ≥10% positive tumor cells with nuclear staining. Ki-67 was classified into the following three groups: low (<20%), intermediate (20-50%) and high (≥50%), and the p53 high group was indicated by ≥50% staining. RFS was compared according to the level of Ki-67 and p53. Results: Patients with a high Ki-67 value were frequently seen in 53% of the cases with TNBC (luminal: 6% and HER2 disease: 25%, p<0.0001). The greatest proportion of patients in the low p53 group were the luminal type (luminal: 7%, HER2 disease: 49%, TNBC: 54%, p<0.0001). A high Ki-67 value was not associated with poor RFS in TNBC (p=0.2734). A high p53 expression was associated with poor RFS (p=0.024). TNBC with adjuvant chemotherapy and a high p53 expression tended to produce poor RFS (p=0.0516). Conclusions: TNBC with a high Ki-67 value was not associated with poor prognosis in this study. However, p53 status could be a significant prognostic factor in TNBC patients, especially in adjuvant chemotherapy cases.

Survivin as a Useful Adjunct Marker for the Grading of Papillary Urothelial Carcinoma

2008 ◽  
Vol 132 (2) ◽  
pp. 224-231
Author(s):  
Ying-bei Chen ◽  
Jiangling J. Tu ◽  
Jean Kao ◽  
Xi K. Zhou ◽  
Yao-Tseng Chen
Keyword(s):  
Urothelial Carcinoma ◽  
Messenger Rna ◽  
Interobserver Variability ◽  
World Health ◽  
Low Grade ◽  
Nuclear Staining ◽  
High Grade ◽  
Grade Group ◽  
Ki 67 ◽  
Papillary Urothelial Carcinoma

Abstract Context.—Distinguishing low-grade and high-grade noninvasive papillary urothelial carcinoma based on morphologic criteria can be challenging and adjunct markers are highly desirable. Survivin, presumably an antiapoptotic protein, was previously proposed as a prognostic marker for urothelial carcinoma. Objective.—To assess interobserver variability by 2004 World Health Organization classification and the value of survivin and Ki-67 as potential markers for grading noninvasive papillary urothelial carcinoma. Design.—Fifty-one bladder biopsies were graded blindly by 5 experienced general surgical pathologists. The protein and messenger RNA expression of survivin and Ki-67 was evaluated by immunohistochemistry and quantitative reverse transcription–polymerase chain reaction using paraffin-embedded tissue. The immunohistochemistry result was quantitatively analyzed using a computer-based color deconvolution module. Results.—The diagnostic agreement among 5 pathologists was fair to poor, with 32% of the cases graded differently by at least 2 raters. All cases were divided into 3 groups: consensus low-grade, consensus high-grade, and indeterminate. The percentage of urothelial cells with positive survivin nuclear staining (survivin score) was significantly higher in the high-grade than in the low-grade group (P &lt; .001). Survivin score outperformed Ki-67 in separating the high-grade group from the low-grade group and showed a significantly higher predictive accuracy for high-grade recurrence than the histologic grade. The disagreement of grading for the indeterminate group could be resolved by their survivin scores in most cases. Survivin messenger RNA level correlated well with survivin score by immunohistochemistry but was not a more discriminating marker. Conclusions—Significant interobserver variability exists in grading low-grade versus high-grade papillary urothelial carcinoma. Survivin immunohistochemical staining can be a useful adjunct tool for the grading of challenging cases.

scholarly journals BRCA1 and MAD2 Are Coexpressed and Are Prognostic Indicators in Tubo-ovarian High-Grade Serous Carcinoma

2018 ◽  
Vol 28 (3) ◽  
pp. 472-478 ◽  
Author(s):  
Tara Byrne ◽  
Laura Nelson ◽  
James P. Beirne ◽  
Daniel Sharpe ◽  
Jennifer E. Quinn ◽  
...  
Keyword(s):  
Overall Survival ◽  
Staining Intensity ◽  
Prognostic Indicators ◽  
Serous Carcinoma ◽  
Nuclear Staining ◽  
High Grade ◽  
Strongly Correlated ◽  
Brca1 Expression ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded

ObjectivesThe aim of this study was to investigate the relationship between BRCA1 and mitotic arrest deficiency protein 2 (MAD2) protein expression, as determined by immunohistochemistry, and clinical outcomes in epithelial ovarian carcinoma (EOC).MethodsA tissue microarray consisting of 94 formalin-fixed paraffin-embedded EOC with fully matched clinicopathological data were immunohistochemically stained with anti-BRCA1 and anti-MAD2 antibodies. The cores were scored in a semiquantitative manner evaluating nuclear staining intensity and extent. Coexpression of BRCA1 and MAD2 was evaluated, and patient survival analyses were undertaken.ResultsCoexpression of BRCA1 and MAD2 was assessed in 94 EOC samples, and survival analysis was performed on 65 high-grade serous carcinomas (HGSCs). There was a significant positive correlation between BRCA1 and MAD2 expression in this patient cohort (P < 0.0001). Both low BRCA1 and low MAD2 are independently associated with overall survival because of HGSC. Low coexpression of BRCA1 and MAD2 was also significantly associated with overall survival and was driven by BRCA1 expression.ConclusionBRCA1 and MAD2 expressions are strongly correlated in EOC, but BRCA1 expression remains the stronger prognostic factor in HGSC.

scholarly journals Expression of Ki-67 and Its Association with Histological Type, Grade and Stage of Colorectal Carcinoma

2021 ◽  
Vol 10 (1-2) ◽  
pp. 33-39
Author(s):  
Sultana Israt Jahan ◽  
Shah Md Badruddoza ◽  
SM Asafudullah ◽  
Md Nurul Amin
Keyword(s):  
Colorectal Carcinoma ◽  
Curve Analysis ◽  
Proliferation Index ◽  
Low Grade ◽  
High Grade ◽  
Roc Curve Analysis ◽  
Ki 67 ◽  
Medical College ◽  
Tissue Sections ◽  
Dukes Staging

Background & objective: The role Ki-67 as a prognostic marker has been studied in many cancers in many studies. However, only few studies reported the prognostic role of Ki-67 in colorectal carcinoma (CRC) with contradictory opinions. The present study was undertaken to assess the Ki-67 proliferation index (PI) in tissue sections of CRC and to investigate the relationship between the proliferative activity and histological type, grade and stage of the tumour. Methods: The present cross-sectional descriptive study was conducted in the Department of Pathology, Rajshahi Medical College, Rajshahi over a period of two years from September 2017 to August 2019. All clinically suspected cases of CRC and later confirmed by histopathology were the study population. A total 44 such cases were included in the study. Tissue sections from 44 formalin-fixed and paraffin-embedded tumor specimens were examined at the Department of Pathology of Rajshahi Medical College, Rajshahi. The cases were histologically classified, graded (WHO) and staged according to TNM and modified Dukes’ staging system. Ki-67 proliferation index was calculated immunohistochemically using the monoclonal antibody MIB-1, and were studied under light microscope. Expression of Ki-67 was calculated as a percentage of labeled nuclei per 500 cells counted in consecutive five high-power fields in the most reactive areas of the slides. The staining results were categorized into groups using a cut-off value of Ki-67 determined by ROC curve analysis. Results: In the present study the cases with high Ki-67 PI were significantly associated with high grade colorectal carcinoma (p = 0.005). TNM Stage-II and Stage-III tumours were more likely to be associated with high Ki-67 PI than those with low Ki-67 PI (p < 0.001). A significant association was observed between Ki-67 immuno-expression and modified Dukes’ staging of the tumours with Stage C being highly associated with high Ki-67 PI (p < 0.001). But histologic tumor type (mucinous and non-mucinous) was not found to be associated with Ki-67 proliferation index. Based on Receiver Operating Characteristic (ROC) curve analysis tumors with nuclear immunoreactivity ≥ 25% were considered as high proliferation index (PI) and < 25% as low PI. The Ki-67 at a cut-off value of >25% had high sensitivity (85.7%) in differentiating high grade CRC from the low-grade tumors but its specificity was moderate (67.6%) with overall diagnostic accuracy being 70.5%. Conclusion: The study concluded that cases with high Ki-67 PI are significantly associated with high grade CRC (poorly differentiated) than the cases with low grade CRC (well and moderately differentiated). TNM Stage-II & Stage-III and modified Dukes’ stage C also more often tend to be associated with high Ki-67 PI than with low Ki-67 PI. Ibrahim Card Med J 2020; 10 (1&2): 33-39

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