Salvatore Lopez

Carcinosarcomas (CSs) of the uterus and ovary are highly aggressive neoplasms containing both carcinomatous and sarcomatous elements. We analyzed the mutational landscape of 68 uterine and ovarian CSs by whole-exome sequencing. We also performed multiregion whole-exome sequencing comprising two carcinoma and sarcoma samples from six tumors to resolve their evolutionary histories. The results demonstrated that carcinomatous and sarcomatous elements derive from a common precursor having mutations typical of carcinomas. In addition to mutations in cancer genes previously identified in uterine and ovarian carcinomas such as TP53, PIK3CA, PPP2R1A, KRAS, PTEN, CHD4, and BCOR, we found an excess of mutations in genes encoding histone H2A and H2B, as well as significant amplification of the segment of chromosome 6p harboring the histone gene cluster containing these genes. We also found frequent deletions of the genes TP53 and MBD3 (a member with CHD4 of the nucleosome remodeling deacetylase complex) and frequent amplification of chromosome segments containing the genes PIK3CA, TERT, and MYC Stable transgenic expression of H2A and H2B in a uterine serous carcinoma cell line demonstrated that mutant, but not wild-type, histones increased expression of markers of epithelial-mesenchymal transition (EMT) as well as tumor migratory and invasive properties, suggesting a role in sarcomatous transformation. Comparison of the phylogenetic relationships of carcinomatous and sarcomatous elements of the same tumors demonstrated separate lineages leading to these two components. These findings define the genetic landscape of CSs and suggest therapeutic targets for these highly aggressive neoplasms.

INTRODUCTION: Ovarian cancer is the leading cause of death from gynecologic cancers, in fact, >80% of cases are diagnosed as advanced-stage disease associated with a high mortality rate (<40% of women cured). A systematic review was performed to estimate the role of HE4 in the diagnosis, prognosis and follow-up of ovarian tumors. Areas covered: A comprehensive search of the literature from January 1952 to August 2016 was conducted using the terms 'ovarian tumor' and 'ovarian cancer' combined with 'HE4' and 'human epididymis protein 4'. The search identified a total of 259 citations, of which 141 were potentially relevant after initial evaluation. Of these studies, 75 primary studies met the inclusion criteria and were analyzed, with a total of 14,773 patients. Expert commentary: Serum HE4 dosage is a useful preoperative test for predicting the benign or malignant nature of pelvic masses. It seems to have a promising role in the prediction of clinical and surgical outcomes. Moreover, HE4 seems to better predict recurrence in comparison to CA-125.

Endometriosis is a condition characterized by the presence of endometrial tissue outside the uterine cavity, leading to a chronic inflammatory reaction. It is one of the most widespread gynecological diseases with a 10-15% prevalence in the general female population, rising up to 30-45% in patients with infertility. Although it was first described in 1860, its etiology and pathogenesis are still unclear. It is now accepted that inflammation plays a central role in the development and progression of endometriosis. In particular, it is marked by an inflammatory process associated with the overproduction of an array of inflammatory mediators such as prostaglandins, metalloproteinases, cytokines, and chemokines. In addition, the growth and adhesion of endometrial cells in the peritoneal cavity due to reactive oxygen species (ROS) and free radicals lead to disease onset, its ensuing symptoms-among which pain and infertility. The aim of our review is to evaluate the role of oxidative stress and ROS in the pathogenesis of endometriosis and the efficacy of antioxidant therapy in the treatment and mitigation of its symptoms.