Endometriosis, Leiomyoma and Adenomyosis: the Risk of Gynecologic Malignancy

The aim of this review article was to evaluate the relationship and the possible etiological mechanismsbetween endometriosis, leiomyoma (LM) and adenomyosis and gynecological cancers, such as ovarian andendometrial cancer and leiomyosarcoma (LMS). MEDLINE was searched for all articles written in the Englishliterature from July 1966 to May 2013. Reports were collected systematically and all the references were alsoreviewed. Malignant transformation of gynecologic benign diseases such as endometriosis, adenomyosis and LMto ovarian and endometrial cancer remains unclear. Hormonal factors, inflammation, familial predisposition,genetic alterations, growth factors, diet, altered immune system, environmental factors and oxidative stressmay be causative factors in carcinogenesis. Early menarche, low parity, late menopause and infertility havealso been implicated in the pathogenesis of these cancers. Ovarian cancers and endometriosis have been shownto have common genetic alterations such as loss of heterozygosity (LOH), PTEN, p53, ARID1A mutations.MicroRNAs have also been implicated in malignant transformation. Inflammation releases proinflammatorycytokines, and activates tumor associated macrophages (TAMS) and nuclear factor kappa b (NF-KB) signalingpathways that promote genetic mutations and carcinogenesis. MED12 mutations in LM and smooth muscletumors of undetermined malignant potential (STUMP) may contribute to malignant transformation to LMS.A hyperestrogenic state may be shared in common with pathogenesis of adenomyosis, LM and endometrialcancer. However, the effect of these benign gynecologic diseases on endometrial cancer should be studied indetail. This review study indicates that endometriosis, LM, adenomyosis may be associated with increased riskof gynecological cancers such as endometrial and ovarian cancers. The patients who have these gynecologicalbenign diseases should be counseled about the future risks of developing cancer. Further studies are neededto investigate the relationship between STUMPs, LMS and LM and characteristics and outcome endometrialcarcinoma in adenomyotic patients.