Evaluating the K-ras mutation in Endometriosis-associated Borderline and Malignant Epithelial Ovarian Tumors

Introduction: Endometriosis is a common gynecological disorder affecting about 10% of women in their childbearing ages. Although endometriosis is considered as a benign condition, it can present with malignant features such as metastasis or invasion. Various studies have evaluated this matter after the first suspected transformation of endometriosis to malignancy was reported, and their findings have shown a higher risk of ovarian cancer in patient with endometriosis. Nevertheless, no concrete conclusion has been reached on the relation between K-ras mutation and ovarian endometrioid or clear cell carcinomas. Materials and Methods: In this cross-sectional study, all the patients with epithelial borderline and malignant ovarian carcinomas who underwent oophorectomy or hysterectomy in Yas and Imam Khomeini Hospitals during 2004-2014 were identified and their specimens were re-evaluated regarding the type of tumor, differentiation and simultaneous presence of endometriosis or atypical endometriosis. After confirming the diagnosis, paraffin blocks were obtained for DNA extraction via polymerase chain reaction, and the samples were tested for mutation in codons 12 and 13. Gathered data were recorded and entered into SPSS v.22 for data analysis.Results: A total of 42 patients with an average age of 43.0±11.3 years old were included. DNA genome extraction was done in 36 cases, in which K-ras mutation was identified in 6 samples (16.7%). Endometriosis was present in 27 patients (64.3%) and 12 subject were found to have atypical endometriosis (28.6%). Squamous metaplasia was observed in 11 subjects (26.2%). Based on their medical records, 2 patients expired (7.4%). The mean survival after surgery was calculated to be 54.3±3.9 months. Frequency of K-ras mutation was found to be significantly lower in patients with positive endometriosis (p=0.024). Moreover, presence of squamous metaplasia was found to be significantly correlated with mortality of patients (p=0.043). Conclusion: The results of this study showed a significant association between K-ras mutation in epithelial ovarian tumors with 10-50% endometriosis; the wide range is due to the limited sample size. Currently this correlation has been reported as 16.6% which has not been found to be statistically significant; compared to previous studies, although this survey has a lower power due to the small sample size but the variety in our samples can be clearly seen. Moreover, 4 out of the 6 cases with mutations were associated with endometriosis; a previously established relation.

Keywords:

ovarian borderline epithelial tumors , , Endometrioid carcinoma , Clear cell carcinoma , K-ras mutation , endometriosis , atypical endometriosis