The
Cancer Genome Atlas has reported that 96% of ovarian high-grade serous
carcinomas (HGSCs) have TP53 somatic mutations suggesting that mutation of this gene is a defining feature of this
neoplasm. In the current study, 5 gynecologic pathologists independently evaluated
hematoxylin and
eosin slides of 14 available cases from The
Cancer Genome Atlas classified as HGSC that lacked a TP53 mutation. The histologic diagnoses rendered by these pathologists and the accompanying molecular genetic data are the subject of this report. Only 1 case (Case 5), which contained a homozygous deletion of TP53, had unanimous interobserver agreement for a diagnosis of pure HGSC. In 1 case (Case 3), all 5 observers (100%) rendered a diagnosis of HGSC; however, 3 observers (60%) noted that the histologic features were not classic for HGSC and suggested this case may have arisen from a low-grade serous
carcinoma (arisen from an alternate pathway compared with the usual HGSC). In 2 cases (Cases 4 and 12), only 3 observers (60%) in each case, respectively, interpreted it as having a component of HGSC. In the remaining 10 (71%) of
tumors (Cases 1, 2, 6-11, 13, and 14), the consensus diagnosis was not HGSC, with individual diagnoses including low-grade serous
carcinoma, high-grade
endometrioid carcinoma, HGSC, metastatic
carcinoma, clear cell
carcinoma, atypical proliferative (borderline) serous
tumor, and
adenocarcinoma, not otherwise specified. Therefore, 13 (93%) of the
tumors (Cases 1-4 and 6-14) were either not a pure HGSC or represented a diagnosis other than HGSC, all with molecular results not characteristic of HGSC. Accordingly, our review of the TP53 wild-type HGSCs reported in The
Cancer Genome Atlas suggests that 100% of de novo HGSCs contain TP53 somatic mutations or deletions, with the exception of the rare HGSCs that develop from a low-grade serous
tumor precursor. We, therefore, propose that lack of molecular alterations of TP53 are essentially inconsistent with the diagnosis of ovarian HGSC and that
tumors diagnosed as such should be rigorously reassessed to achieve correct classification.