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Exp Mol Pathol. 2013 Oct;95(2):235-41. doi: 10.1016/j.yexmp.2013.08.004. Epub 2013 Aug 18.

TP53 mutations are common in all subtypes of epithelial ovarian cancer and occur concomitantly with KRAS mutations in the mucinous type.

Author information

1
Institute of Surgical Pathology, University Hospital Zurich, Switzerland.

Abstract

AIMS:

Epithelial ovarian cancer (EOC) can be classified into four major types (serous, endometrioid, clear cell, mucinous). The prevalence of driver gene mutations in the different subtypes is controversial. High-grade serous carcinomas show frequent TP53 mutations, whereas KRAS and BRAF mutations are less common. In non-serous EOC, the relevance of these gene mutations remains to be elucidated.

METHODS:

We investigated 142 formalin-fixed, paraffin-embedded EOC, including serous (n=63), endometrioid (n=29), clear cell (n=25), mucinous (n=14), and others (n=11) for mutations in TP53 exons 5-8, KRAS exons 2 and 3, and BRAF exon 15 by pyro-sequencing using the GS Junior 454 platform. The mutational status was correlated with clinicopathological features and patient overall survival.

RESULTS:

We identified mutations in the coding region of TP53 in 51.4% (73/142), and of KRAS in 9.9% (14/142) but not of BRAF. TP53 mutations occurred frequently not only in high-grade serous carcinomas (58.7%), but also in mucinous (57%) and clear cell EOC (52%). TP53 mutations were associated with high-grade carcinomas (p=0.014), advanced FIGO stage (p=0.001), intraoperative residual disease >1cm (p=0.004), as well as poor overall survival (p=0.002). KRAS mutations were mainly identified in mucinous EOC (57%) and were concomitantly with TP53 mutations in five mucinous carcinomas (36%).

CONCLUSIONS:

TP53 gene driver mutations are a common feature of all advanced ovarian cancer subtypes, whereas BRAF mutations seem to be a rare event in EOC. KRAS mutations with synchronous TP53 mutations occur predominantly in low-grade mucinous carcinomas, suggesting a specific molecular background of this ovarian cancer type.

KEYWORDS:

BRAF; Deep-sequencing; Epithelial ovarian cancer; KRAS; TP53

PMID:
23965232
DOI:
10.1016/j.yexmp.2013.08.004
[Indexed for MEDLINE]

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