The Role of Oxidative Stress and Membrane Transport Systems during Endometriosis: A Fresh Look at a Busy Corner

Table 2

Major genetic alterations/mutations in different stages of endometriosis associated ovarian cancer (EAOC).

Factor	Genetic alteration	Current data
Tumor suppressor genes	PTEN	Phosphatase and tensin homolog is mutated in many cancers, particularly in endometrial and endometrioid ovarian cancer; its inactivation occurs early during tumorigenesis [102]. PTEN somatic mutations are frequently found in endometriotic cysts [101].
	ARID1A	ARID1A mutations are significantly more common in two ovarian cancer subtypes associated with endometriosis (clear cell and endometrioid). Endometriosis synchronous with ovarian cancer presented more frequent mutations in clones derived from endometriosis samples directly adjacent of the tumor than in those from distant endometriotic lesions [104].
DNA repair	hMLH1	hMLH1 corrects errors in DNA replication; hypermethylation of its promoter occurs early in endometriosis malignant transformation [102].
Loss of heterozygosity (LOH)		A trend to increased LOH frequencies has been reported in solitary endometriosis lesions, endometriosis-associated carcinoma, and endometrioid ovarian cancer. Common LOH events can be identified in endometriosis synchronous with ovarian cancer [101].
	ARID1A and PIK3CA	ARID1A and PIK3CA mutations were found in ovarian clear cell carcinoma and in tumor-adjacent and distant endometriotic lesions, regardless of cytological atypia [112–114].
	ARID1A and p53	Both ARID1A and p53 were mutually altered in pure-type clear cell carcinoma at immunohistochemical analysis. Altered expression of p53 in these clear cell carcinomas was associated with significant worse prognosis than that of ARID1A () [115].
	β-Catenin	β-Catenin mutations and overexpression are very common in ovarian endometrioid carcinoma; approximately 50% of endometrioid carcinoma has β-catenin alterations [116]. Endometrioid carcinoma containing β-catenin mutations is low grade and associated with better prognosis. As many as 90% of endometrioid borderline tumors harbor β-catenin mutations.