Biological significance of KRAS mutant allele expression in ovarian endometriosis

Nozomi Yachida, Kosuke Yoshihara, Kazuaki Suda, Hirofumi Nakaoka, Haruka Ueda, Kentaro Sugino, Manako Yamaguchi, Yutaro Mori, Kaoru Yamawaki, Ryo Tamura, Tatsuya Ishiguro, Hiroaki Kase, Teiichi Motoyama, Takayuki Enomoto
Cancer science · 2021 · vol. 112(5) , pp. 2020–2032 · doi:10.1111/cas.14871 · PMID:33675098 · PMC8088964 · W3135669164
article OA: gold CC0 ⤵ 16 in-corpus citations
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This study detected KRAS p.G12V mutant allele expression in ovarian endometriosis, finding it associated with inflammation and intratumor heterogeneity, unlike its diffuse pattern in ovarian cancer.

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Abstract

KRAS is the most frequently mutated in ovarian endometriosis. However, it is unclear whether the KRAS mutant allele's mRNA is expressed and plays a biological role in ovarian endometriosis. Here, we performed mutation-specific RNA in situ hybridization to evaluate mutant allele expression of KRAS p.G12V, the most frequently detected mutation in ovarian endometriosis in our previous study, in formalin-fixed paraffin-embedded tissue (FFPE) samples of ovarian endometriosis, cancer cell lines, and ovarian cancers. First, we verified that mutant or wild-type allele of KRAS were expressed in all 5 cancer cell lines and 9 ovarian cancer cases corresponding to the mutation status. Next, we applied this assay to 26 ovarian endometriosis cases, and observed mutant allele expression of KRAS p.G12V in 10 cases. Mutant or wild-type allele of KRAS were expressed in line with mutation status in 12 available endometriosis cases for which KRAS gene sequence was determined. Comparison of clinical features between ovarian endometriosis with KRAS p.G12V mutant allele expression and with KRAS wild-type showed that KRAS p.G12V mutant allele expression was significantly associated with inflammation in ovarian endometriosis. Finally, we assessed the spatial distribution of KRAS mutant allele expression in 5 endometriosis cases by performing multiregional sampling. Intratumor heterogeneity of KRAS mutant allele expression was observed in two endometriosis cases, whereas the spatial distribution of KRAS p.G12V mutation signals were diffuse and homogenous in ovarian cancer. In conclusion, evaluation of oncogene mutant expression will be useful for clarifying the biological significance of oncogene mutations in benign tumors.

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Condition tags

endometriosis

MeSH descriptors

Alleles Endometriosis Gene Expression Genes, ras In Situ Hybridization Mutation Ovarian Diseases Adult Cell Line Endometriosis Endometriosis Female Humans In Situ Hybridization Laser Capture Microdissection Mitogen-Activated Protein Kinase Kinases Mitogen-Activated Protein Kinase Kinases Ovarian Diseases Ovarian Diseases Ovarian Neoplasms

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