Novel insights on the malignant transformation of endometriosis into ovarian carcinoma

The malignant transformation of endometriosis is an uncommon event, which happens in 0.7-2.5% of the cases, and, when occurs, it usually involves the ovary. A 2 to 3-fold higher risk of ovarian endometrioid and clear cell carcinoma has been reported in women with endometriosis. Pathological studies have detected a morphological continuum of sequential steps from normal endometriotic cyst epithelium to atypical endometriosis and finally to invasive carcinoma. Ovarian endometrioid carcinoma harbors mutations of CTNNB1 in 16-53.3%, of PTEN in 14-20% and of ARID1A in 30-55% of the cases. Ovarian clear cell carcinoma harbors mutations of PIK3CA in 20-40% and of ARID1 in 15-75% of the cases. Whereas estrogen receptors and progesterone receptors are quite always absent, HNF-1b is often over-expressed in this histotype. Atypical endometriosis and endometriosis-related ovarian neoplasms share molecular alterations, such as PTEN mutations, ARID1A mutations and up-regulation of HNF-1b. Moreover, ARID1A mutations have been noted in clear cell tumors and contiguous atypical endometriosis, but not in distant endometriotic lesions. The loss of BAF250a protein expression is suggestive for the presence of ARID1A mutations, and represents an useful marker of malignant transformation of endometriosis.