Gene mutations that are generally thought to be related to cancer, including KRAS, are being found with increasing frequency in endometriosis. This is concerning, yet potentially very helpful in the long run to help identify those at risk for endometriosis-related cancer vs those who are not. The following study results were recently published.
“KRAS is the most commonly mutated gene found in ovarian endometriosis. However, it is unclear whether the mRNA of the KRAS mutated allele is expressed and whether it plays a biological role in ovarian endometriosis. Here we performed mutation-specific RNA in situ hybridization to assess the mutated allele expression of KRAS p.G12V, the mutation most commonly detected in ovarian endometriosis in our previous study, in formalin-fixed paraffin-embedded tissue samples (FFPE) of ovarian endometriosis, cancer cell lines and ovarian cancer.
First, we checked that the mutated or wild-type allele of KRAS was expressed in all 5 cancer cell lines and 9 cases of ovarian cancer according to the mutation status. We next applied this assay to 26 cases of ovarian endometriosis and observed mutant allele expression of KRAS p.G12V in 10 cases. The mutated or wild-type allele of KRAS was expressed according to the mutation status in 12 available endometriosis cases for which the KRAS gene sequence was determined. A comparison of the clinical features between the endometriosis of the ovaries with the mutated KRAS p.G12V allele expression and the KRAS wild type showed that the mutated KRAS p.G12V allele expression was significantly associated with inflammation in the endometriosis of the ovaries.
Finally, we investigated the spatial distribution of the expression of KRAS mutated alleles in 5 endometriosis cases by performing multi-regional sampling. Intratumoral heterogeneity of the KRAS mutated allele expression was observed in two endometriosis cases, while the spatial distribution of the KRAS p.G12V mutation signals in ovarian cancer was diffuse and homogeneous.
In conclusion, the evaluation of the expression of oncogene mutants will be useful to clarify the biological significance of oncogene mutations in benign tumors and processes like endometriosis.”