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Several available studies have already analyzed the systemic effects of endocrine-disrupting chemicals (EDCs) on fertile woman and neonatal outcomes, but little is still known in humans about the precise mechanisms of interference of these compounds with the endometrial receptivity. There is consistent evidence that continuous and prolonged exposure to EDCs is a risk factor for reduced fertility and fecundity in women. Preliminary studies on mammalian models provide robust evidence about this issue and could help gynecologists worldwide to prevent long term injury caused by EDCs on human fertility. In this systematic review, we aimed to systematically summarize all available data about EDC effects on blastocyst endometrial implantation. We performed a systematic review using PubMed®/MEDLINE® to summarize all in vivo studies, carried out on mice models, analyzing the molecular consequences of the prolonged exposure of EDC on the implantation process. 34 studies carried out on mouse models were included. Primary effects of EDC were a reduction of the number of implantation sites and pregnancy rates, particularly after BPA and phthalate exposure. Furthermore, the endometrial expression of estrogen (ER) and progesterone receptors (PR), as well as their activation pathways, is compromised after EDC exposure. Finally, the expression of the primary endometrial markers of receptivity (such as MUC1, HOXA10, Inn and E-cadherin) after EDC contact was analyzed. In conclusion EDC deeply affect blastocyst implantation in mouse model. Several players of the implantation mechanism are strongly influenced by the exposure to different categories of EDC.

Simple Summary The aim of the present meta-analysis was to analyze all available studies reporting clinical characteristics of breast cancer gene 1 (BRCA1) gene hypermethylated breast cancer in women, and to pool the results in order to provide a unique clinical profile of this cancer setting population. Identifying the clinical profile of breast cancer in women harboring BRCA1 gene hypermethylation may help oncologists select a subgroup of patients who may be candidates for BRCA1 methylation assessment, thus, possibly enlarging the cancer population who may benefit from new target-therapy agents. Results showed that BRCA1 gene hypermethylation should be suspected in all breast cancer patients with advanced disease stages, positive lymph nodes, and premenopausal age at diagnosis. Multidisciplinary groups treating women with breast cancer should take into account the possibility of addressing patients with these characteristics with a BRCA1 gene methylation status analysis. Abstract Background: DNA aberrant hypermethylation is the major cause of transcriptional silencing of the breast cancer gene 1 (BRCA1) gene in sporadic breast cancer patients. The aim of the present meta-analysis was to analyze all available studies reporting clinical characteristics of BRCA1 gene hypermethylated breast cancer in women, and to pool the results to provide a unique clinical profile of this cancer population. Methods: On September 2020, a systematic literature search was performed. Data were retrieved from PubMed, MEDLINE, and Scopus by searching the terms: “BRCA*” AND “methyl*” AND “breast”. All studies evaluating the association between BRCA1 methylation status and breast cancer patients’ clinicopathological features were considered for inclusion. Results: 465 studies were retrieved. Thirty (6.4%) studies including 3985 patients met all selection criteria. The pooled analysis data revealed a significant correlation between BRCA1 gene hypermethylation and advanced breast cancer disease stage (OR = 0.75: 95% CI: 0.58–0.97; p = 0.03, fixed effects model), lymph nodes involvement (OR = 1.22: 95% CI: 1.01–1.48; p = 0.04, fixed effects model), and pre-menopausal status (OR = 1.34: 95% CI: 1.08–1.66; p = 0.008, fixed effects model). No association could be found between BRCA1 hypermethylation and tumor histology (OR = 0.78: 95% CI: 0.59–1.03; p = 0.08, fixed effects model), tumor grading (OR = 0.78: 95% CI :0.46–1.32; p = 0.36, fixed effects model), and breast cancer molecular classification (OR = 1.59: 95% CI: 0.68–3.72; p = 0.29, random effects model). Conclusions: hypermethylation of the BRCA1 gene significantly correlates with advanced breast cancer disease, lymph nodes involvement, and pre-menopausal cancer onset.

Breast cancer (BC) is the most common malignancy in women worldwide. Breast cancer related mortality has dropped significantly since the widespread adoption of mammographic screening. Approximately, 5% of the patients with BC carry germline mutations that are responsible for their condition. Women carrying a BRCA 1 or 2 mutation have a 57% and 49% lifetime risk of developing breast cancer, respectively. For BRCA1/2 patients reluctant to a prophylactic surgery, the only risk reducing strategy remains an increased imaging and clinical surveillance. Whereas a closer screening mammogram program is helpful in detecting BC at an earlier stage, no laboratory markers exist. New markers would be helpful in identifying BC, once the mutations are identified, and in monitoring the cancer behavior and response to treatment, once the cancer is diagnosed. MicroRNAs (miRNAs) are key regulatory molecules operating in a post-transcriptional level by regulating gene expression. Aberrant miRNA expression was documented in several pathological conditions, including solid tumors, suggesting their involvement in tumorigenesis. MiRNAs can be detected in human fluids and could be used as biomarkers. A different pattern expression of miRNA in biological fluids of BC patients as compared to healthy control is currently under consideration in many clinical trials. The biologic mechanism of miRNAs, a rationale of its use as biomarker in cancer, and a literature review of the most significant results achieved about miRNAS in BC will be reported and discussed in this chapter.

Breast cancer is the most common malignancy in women worldwide, and ovarian cancer is the most lethal gynecological malignancy. Women carrying a BRCA1/2 mutation have a very high lifetime risk of developing breast and ovarian cancer. The only effective risk-reducing strategy in BRCA-mutated women is a prophylactic surgery with bilateral mastectomy and bilateral salpingo-oophorectomy. However, many women are reluctant to undergo these prophylactic surgeries due to a consequent mutilated body perception, unfulfilled family planning, and precocious menopause. In these patients, an effective screening strategy is available only for breast cancer, but it only consists in close radiological exams with a significant burden for the health system and a significant distress to the patients. No biomarkers have been shown to effectively detect breast and ovarian cancer at an early stage. MicroRNAs (miRNAs) are key regulatory molecules operating in a post-transcriptional regulation of gene expression. Aberrant expression of miRNAs has been documented in several pathological conditions, including solid tumors, suggesting their involvement in tumorigenesis. miRNAs can be detected in blood and urine and could be used as biomarkers in solid tumors. Encouraging results are emerging in gynecological malignancy as well, and suggest a different pattern of expression of miRNAs in biological fluids of breast and ovarian cancer patients as compared to healthy control. Aim of this study is to highlight the role of the urinary miRNAs which are specifically associated with cancer and to investigate their role in early diagnosis and in determining the prognosis in breast and ovarian cancer.

Purposes: Congenital uterine anomalies (CUA) are benign conditions associated with relatively serious complications affecting the reproductive life. Due to their infrequency CUA are often misdiagnosed, exposing the patient to possible future complications. Case description: We report the cases of three women affected by an unknown CUA, which underwent three different diagnostic and surgical approaches. Conclusions: A correct and early diagnosis of CUA is mandatory to allow a correct clinical and therapeutic management. In our opinion we might avoid the use of MRI considered as the second line technique after 2D-US, keeping in mind that in CUA the diagnostic value of 3D-US has the same accuracy as MRI.

Cervicalcancerisolatedsplenicrecurrenceisarareevent.Wereportacaseofspleniccervicalcancermetastasistreated with salvage surgery 30 months after supralevator anterior pelvic exenteration. In this patient theplasmatic level of squamous cell carcinoma antigen increased in the absence of any evidence of disease at theinstrumental examination 24 months after surgery. Surgery had a high impact on quality of life. Key words: cervical cancer, splenic metastasis, unusual metastasis. Introduction Cervical cancer is the second most common malig-nancy among women worldwide, with an estimatedincidence of 493 000 new cases and 274 000 deaths inthe year 2002. 1 Patients with recurrent disease or pelvicmetastases have a poor prognosis with a 1-year sur-vival rate ranging between 15 and 20%. 2 The site ofrecurrence (local or distant) is strictly correlated withstages classified by the International Federation ofGynecology and Obstetrics (FIGO), with a preponder-ance of local recurrence in the early stages and distantor local plus distant recurrence in advanced cases.