Header

UZH-Logo

Maintenance Infos

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


Rechsteiner, Markus; Zimmermann, Anne-Katrin; Wild, Peter J; Caduff, Rosmarie; von Teichman, Adriana; Fink, Daniel; Moch, Holger; Noske, Aurelia (2013). TP53 mutations are common in all subtypes of epithelial ovarian cancer and occur concomitantly with KRAS mutations in the mucinous type. Experimental and Molecular Pathology, 95(2):235-241.

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 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.

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 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.

Statistics

Citations

23 citations in Web of Science®
24 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 27 Aug 2013
0 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Gynecology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:27 Aug 2013 12:23
Last Modified:07 Dec 2017 22:09
Publisher:Elsevier
ISSN:0014-4800
Publisher DOI:https://doi.org/10.1016/j.yexmp.2013.08.004
PubMed ID:23965232

Download