Biological significance of KRAS mutant allele expression in ovarian endometriosis. Issue 5 (30th March 2021)

• Record Type: Journal Article
• Authors: Yachida, Nozomi; Yoshihara, Kosuke; Suda, Kazuaki; Nakaoka, Hirofumi; Ueda, Haruka; Sugino, Kentaro; Yamaguchi, Manako; Mori, Yutaro; Yamawaki, Kaoru; Tamura, Ryo; Ishiguro, Tatsuya; Kase, Hiroaki; Motoyama, Teiichi; Enomoto, Takayuki
• Is Part Of: Cancer science. Volume 112:Issue 5(2021)
• Page Start: 2020
• Page End: 2032
• Publication Date: 2021-03-30
• Subjects: endometriosis -- in situ hybridization -- intratumor heterogeneity -- KRAS -- mutant allele expression; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14871
• Languages: English
• ISSNs: 1347-9032

Abstract

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. Abstract : We could visualize mutant allele expression of KRAS p.G12V in ovarian endometriosis epithelial cells harboring KRAS p.G12V mutation by using the in‐situ hybridization assay and revealed biological significance of KRAS mutant allele expression in ovarian endometriosis.