Histologic subclassification of high-grade
endometrial carcinomas can sometimes be a diagnostic challenge when based on histomorphology alone. Here we utilized immunohistochemical markers to determine the immunophenotype in histologically ambiguous high-grade
endometrial carcinomas that were initially diagnosed as pure or mixed high-grade
endometrioid carcinoma, aiming to determine the utility of selected immunohistochemical panel in accurate classification of these distinct
tumor types, while correlating these findings with the clinical outcome. A total of 43 high-grade
endometrial carcinoma cases initially classified as pure high-grade
endometrioid carcinoma (n=32), mixed high-grade
endometrioid carcinoma/serous
carcinoma (n=9) and mixed high-grade
endometrioid carcinoma/clear cell
carcinoma (n=2) were retrospectively stained with a panel of immunostains, including
antibodies for p53, p16,
estrogen receptor, and mammaglobin. Clinical follow-up data were obtained, and stage-to-stage disease outcomes were compared for different
tumor types. Based on aberrant staining for p53 and p16, 17/43 (40%) of the high-grade
endometrial carcinoma cases initially diagnosed as high-grade
endometrioid carcinoma were re-classified as serous
carcinoma. All 17 cases showed negative staining for mammaglobin, while
estrogen receptor was positive in only 6 (35%) cases. The remaining 26 cases of high-grade
endometrioid carcinoma showed wild-type staining for p53 in 25 (96%) cases, patchy staining for p16 in 20 (77%) cases, and were positive for mammaglobin and
estrogen receptor in 8 (31%) and 19 (73%) cases, respectively, thus the initial diagnosis of high-grade
endometrioid carcinoma was confirmed in these cases. In addition, the patients with re-classified serous
carcinoma had advanced clinical stages at diagnosis and poorer overall survival on clinical follow-up compared to that of the remaining 26 high-grade
endometrioid carcinoma cases. These results indicate that selected immunohistochemical panel, including p53, p16, and mammaglobin can be helpful in reaching accurate diagnosis in cases of histomorphologically ambiguous
endometrial carcinomas, and can assist in providing guidance for appropriate therapeutic options for the patients.