No abstract

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.

Dysregulation of microRNA (mi-RNA) expression plays a major role in the development and progression of most human malignancies. Members of the miR-200 family, miR-182, miR-214 and miR-221 are frequently up-regulated, whereas miR-100, let-7i, miR-199a, miR-125b, mir-145 and miR-335 are often down-regulated in ovarian cancer compared with normal ovarian tissue. Most mi-RNA signatures are overlapping in different tumor histotypes but some mi-RNAs seem to be histotype specific. For instance, the endometrioid type shares with the serous and clear cell types the up-regulation of miR-200 family members, but also presents over-expression of miR-21, miR-202 and miR-205. Clear cell carcinoma has a significantly higher expression of miR-30a and miR-30a*, whereas mucinous histotype has elevated levels of miR-192/194. In vitro and in vivo investigations have shown that several mi-RNAs can modulate the sensitivity of ovarian cancer to platinum and taxane, and clinical studies have suggested that mi-RNA profiling may predict the outcome of patients with this malignancy. Some mi-RNAs could be used as biomarkers to identify patients that might benefit from the addition of molecularly targeted agents (i.e. anti-angiogenic agents, MET inhibitors and poly(ADP-ribose) polymerase (PARP) inhibitors) to standard chemotherapy. Moreover, mi-RNAs could represent potential targets for the development of novel therapies.

No abstract

Gestational trophoblastic disease includes complete hydatidiform mole (CHM) or partial hydatidiform mole (PHM) and gestational trophoblastic neoplasia (GTN). Given the very high-curability rate of trophoblastic disease, the risk of further molar pregnancy after CHM or PHM as well as the risk of second primary tumors and fertility compromise after chemotherapy for GTN represent major concerns. The incidence of subsequent molar pregnancy ranges from 0.7 to 2.6% after one CHM or PHM, and is approximately 10% after two previous CHMs. Among patients who have received chemotherapy, there is an increased risk of myeloid leukemia which is mainly related to the cumulative dose of etoposide. Resumption of normal menses occurs in approximately 95% of women treated with chemotherapy, but menopause occurs 3 years earlier compared with those non-treated with chemotherapy. Term live birth rates higher than 70% without increased risk of congenital abnormalities have been reported in these women, and pregnancy outcomes are comparable to those of general population, except a slightly increased risk of stillbirth. Fertility-sparing treatment for placental site trophoblastic tumor is a therapeutic option reserved to highly selected, young women who do not present markedly enlarged uterus or diffuse multifocal disease within the uterus.