Ovarian endometriosis, a precursor of ovarian cancer: Histological aspects, gene expression and microRNA alterations (Review)

Abstract

Ovarian endometriosis is a frequent chronic gynecological disease with an uncertain evolution regarding its progression or association with ovarian malignant lesions. The present review summarized the histological aspects, gene expression and microRNA (miRNA/miR) alterations associated with ovarian endometriosis and cancer and their possible interaction. The endometriosis-ovarian cancer interaction has been proposed by certain researchers as a single entity. Histological results indicated that endometriosis has been in different circumstances coexisting with ovarian cancer, with reference to endometrioid and clear cell carcinoma. Endometriosis with moderate and severe atypia can influence cell proliferation and architecture, resulting in a possible malignant transformation. Gene expression analysis indicated that the pathologies of both endometriosis and ovarian cancer are characterized by genetic instability from a molecular point of view, as several important genetic mutations, including ARID1A, PI3KCA, PTEN, BRCA1, BRCA2, TP53 and KRAS genes, were identified. miRNA alterations have been implicated in the regulation of gene expression. Common dysregulated miRNAs, such as miR-331, miR-335, miR-891, miR-548, miR-124, miR-148, miR-215, miR-192, miR-337, miR-153, miR-155, miR-144, miR-221 and miR-3688 were extensively investigated in understanding endometriosis and ovarian cancer evolution. From a combined viewpoint including histological aspects, gene expression and miRNA alterations, it is reasonable to speculate that endometriosis is associated with ovarian cancer. Ovarian endometriosis lesions may present a risk for ovarian malignant lesions, which supports a model of endometriosis as a malignant precursor. However, the endometriosis-ovarian cancer association is not widely accepted in the literature and additional studies are required to validate this association.

Tubal Endometriosis: From Bench to Bedside, A Scoping Review

“…Histopathologically, the malignant transformation is recognized as cytologic atypia and architectural proliferation [ 10 ]. Cytologic atypia is defined as the transition from benign EM to carcinoma and is classified as moderate (simple hyperplasia or cellular atypia) or severe (complex hyperplasia or cellular atypia that is more evident) [ 11 ]. Concerning cellular proliferation, complex hyperplasia is translated into glandular proliferation and reduced stroma, which can evolve towards ovarian cancer [ 11 ].…”

“…Cytologic atypia is defined as the transition from benign EM to carcinoma and is classified as moderate (simple hyperplasia or cellular atypia) or severe (complex hyperplasia or cellular atypia that is more evident) [ 11 ]. Concerning cellular proliferation, complex hyperplasia is translated into glandular proliferation and reduced stroma, which can evolve towards ovarian cancer [ 11 ]. As mentioned above, endometrioid carcinoma or clear cell carcinoma are the most prevalent types, and their gross appearance consists of the typical histology of each type of malignancy including cribiform, glandular or solid architecture and papillary, solid or tubulocystic architecture for each cancer type, respectively [ 11 ].…”

“…Concerning cellular proliferation, complex hyperplasia is translated into glandular proliferation and reduced stroma, which can evolve towards ovarian cancer [ 11 ]. As mentioned above, endometrioid carcinoma or clear cell carcinoma are the most prevalent types, and their gross appearance consists of the typical histology of each type of malignancy including cribiform, glandular or solid architecture and papillary, solid or tubulocystic architecture for each cancer type, respectively [ 11 ]. Mitoses are also detected in both types.…”

“…Mitoses are also detected in both types. Endometriosis associated ovarian cancer (EAOC) is defined as the coexistence of malignant cells and EM either in the same ovary or EM in the one and cancer in the other ovary [ 10 , 11 ].…”

Screening differentially expressed genes between endometriosis and ovarian cancer to find new biomarkers for endometriosis

“…Several studies have shown that endometriosis is one of the risk factors for ovarian cancer [ 8 ], and a proportion of ovarian cancers have been shown to originate from 0.5 to 1% of cases of ovarian endometriosis [ 9 , 10 ]. Ovarian endometriosis may present a risk for ovarian malignant lesions according to gene expression and miRNA alterations [ 11 , 12 ], and is always managed with the prevention of carcinogenesis [ 13 ]. Immunity and inflammation are thought to be strongly associated with carcinogenicity [ 14 , 15 ]; however, no studies have shown how long ovarian cancer takes to develop from ovarian endometriosis.…”