Tumor cell type can be reproducibly diagnosed and is of independent prognostic significance in patients with maximally debulked ovarian carcinoma

Abstract

Ovarian surface epithelial carcinomas are routinely subclassified by pathologists based on tumor cell type and grade. It is controversial whether cell type or grade is superior in predicting patient response to treatment or survival, in patients stratified by stage of disease. The aim of this study was to uniformly apply updated criteria for cell-type and grade assignment to a series of 575 cases of ovarian surface epithelial carcinoma. All patients were optimally surgically debulked, with no macroscopic residual disease after primary surgery. Slides from these cases were reviewed by a single pathologist, who was blinded to patient outcomes. In 50 cases, 2 additional pathologists reviewed the slides independently to determine interobserver variation in assessment of cell type and grade. The distribution of tumor stage was as follows: stage I--233 cases, stage II--246 cases, stage III--96 cases. The most common cell type encountered was serous carcinoma (229/575, 40%), followed by clear cell (149/575, 26%), endometrioid (139/575, 24%), and mucinous (36/575, 6%). Serous carcinomas were significantly more likely to present with advanced stage disease (76/229 [33.2%] were stage III, and 82% of all stage III tumors were serous), whereas all nonserous cell types were stage I or II at diagnosis in greater than 90% of cases. Both FIGO grade and Silverberg grade stratified patients into groups with significantly different risks of relapse and survival, but the Silverberg grading system was a more powerful prognosticator. In multivariate analysis, stage was the most powerful prognostic indicator (P < .0001), followed by tumor cell type (P = .015), but grade was not of independent significance. Interobserver variation in assignment of cell type was very good (kappa = 0.77) with moderate reproducibility in assignment of Silverberg grade (kappa = 0.40) and minimal reproducibility in assignment of FIGO grade (kappa = 0.27). Thus, in this series of cases of ovarian surface epithelial carcinomas with no macroscopic residual disease after primary debulking surgery, assignment of tumor cell type was both more reproducible and provided superior prognostic information compared with assignment of tumor grade. As tumor cell type also correlates with underlying molecular abnormalities and may predict response to chemotherapy, this suggests that tumor cell type could be used to guide treatment decisions for patients with ovarian surface epithelial carcinoma.