Molecular alterations of TP53 are a defining feature of ovarian high-grade serous carcinoma: A rereview of cases lacking TP53 mutations in The Cancer Genome Atlas Ovarian Study Journal Article
| Authors: | Vang, R.; Levine, D. A.; Soslow, R. A.; Zaloudek, C.; Shih, I. M.; Kurman, R. J. |
| Article Title: | Molecular alterations of TP53 are a defining feature of ovarian high-grade serous carcinoma: A rereview of cases lacking TP53 mutations in The Cancer Genome Atlas Ovarian Study |
| Abstract: | 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. © 2015 International Society of Gynecological Pathologists. |
| Keywords: | clinical article; human tissue; gene mutation; somatic mutation; gene deletion; histopathology; molecular genetics; cancer diagnosis; endometrioid carcinoma; cancer grading; adenocarcinoma; metastasis; wild type; protein p53; homozygosity; ovary carcinoma; eosin; hematoxylin; clear cell carcinoma; tumor classification; pathologist; molecular diagnosis; precancer; tp53; tcga; high-grade serous carcinoma; the cancer genome atlas; human; female; priority journal; article; ovarian high grade serous carcinoma |
| Journal Title: | International Journal of Gynecological Pathology |
| Volume: | 35 |
| Issue: | 1 |
| ISSN: | 0277-1691 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2016-01-01 |
| Start Page: | 48 |
| End Page: | 55 |
| Language: | English |
| DOI: | 10.1097/pgp.0000000000000207 |
| PROVIDER: | scopus |
| PMCID: | PMC4696053 |
| PUBMED: | 26166714 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 February 2016 -- Source: Scopus |
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