Can We Successfully Subtype High Grade Endometrial Carcinomas: The Role of Morphology and Immunohistochemistry Revisited
Cigdem Himmetoglu Ussakli, Alp Usubutun, Dilek Bulbul, Zuhal Isikdogan, Nihan Haberal, Ozlem Ozen, Gaye Guler Tezel. Hacettepe University, Ankara, Turkey; Etlik Zübeyde Hanim Women's Health Education and Research Hospital, Ankara, Turkey; Baskent University, Ankara, Turkey
Background: Endometrial cancer is a common malignancy of the gynecological system and has been classified into 2 groups:Type 1 are estrogen-related,low-grade endometrioid tumors;type 2 are aggressive,high-grade non-endometrioid tumors.The objective of this study was to investigate the usefulness of Ret finger protein(RFP);which we have recently reported to be a marker of serous differentiation and to evaluate the utility of commonly used immunomarkers(ER,PR,p53,p16,Wilms tumor 1(WT-1))for the differentiation of serous endometrial adenocarcinomas from grade 3 endometrioid endometrial carcinomas.
Design: Tissue microarrays constructed from 124 primary endometrial carcinoma cases(24 grade 1 endometrioid,61 grade 3 endometrioid,39 serous) from 3 institutions were evaluated independently by five experienced gynecopathologists.The scoring of immunohistochemical expression was done with compositional method (intensity X percentage of staining) for all the markers. P16 staining was also evaluated in a 2 tier system where diffuse staining in almost 100% of tumor cells was separately noted.Sensitivity,specificity,area under the ROC curve,Kappa statistic and the Kruskal Wallis tests were done for statistical analysis.
Results: Kappa values for interobserver concordance were 0.737 and 0.727 for endometrioid and serous carcinomas respectively(p <0.001).Diffuse p16 staining and p53 emerged as statistically the most sensitive(74% and 74% respectively)and specific(88% and 92% respectively)markers for the differentiation of grade 3 serous from grade 3 endometrioid subtype(p <0.001).ER,PR,WT-1 and RFP did not reach statistical significance for subtyping of grade 3 tumors whereas RFP score was found to be significantly increased in grade 3 endometrial carcinomas compared to grade 1 counterparts(p<0.001).
Conclusions: Grade 3 endometrioid endometrial carcinomas are often lumped together with serous carcinomas as both are high risk tumors.However many studies have shown that they differ with respect to age,stage,and outcome such as extranodal metastasis.In this cohort of high grade endometrioid and serous carcinomas,we were able to reach a strong interobserver concordance and showed that p53 and diffuse p16 staining as the most sensitive and specific immunomarkers for differentiation.In addition we confirmed the selective expression of RFP in high grade endometrial carcinomas compared to grade 1 endometrial cancer.
Category: Gynecologic & Obstetrics
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 177, Monday Morning