Sirtuins participate in hormone imbalance, metabolism and aging, which are important processes for endometrial cancer (EC) development. Sirtuins mRNA expression (SIRT1 to 7) was determined in 76 ECs (63 Type I, 12 Type II and one mixed EC), and 30 non-neoplastic endometria (NNE) by quantitative real-time PCR. SIRT1 and SIRT7 protein expression was evaluated by immunohistochemistry using Allred score. Compared to NNE, ECs showed SIRT7 (p < 0.001) mRNA overexpression, whereas SIRT1 (p < 0.001), SIRT2 (p < 0.001), SIRT4 (p < 0.001) and SIRT5 (p < 0.001) were underexpressed. No significant differences were observed for SIRT3 and SIRT6. Type II ECs displayed lower SIRT1 (p = 0.032) and SIRT3 (p = 0.016) transcript levels than Type I ECs. Concerning protein expression, SIRT1 immunostaining median score was higher in ECs compared to NNE epithelium (EC = 5 vs. NNE = 2, p < 0.001), while SIRT7 was lower in ECs (EC = 6 vs. NNE = 7, p < 0.001). No significant associations were found between SIRT1/7 immunoexpression and histological subtype, grade, lymphovascular invasion or stage. Our data shows that sirtuins are deregulated in EC. The diversity of expression patterns observed suggests that sirtuins may have distinctive roles in endometrial cancer similarly to what has been described in other cancer models.

Peritoneal dissemination is a particular form of metastasis typically observed in ovarian cancer and the major cause for poor patient's outcome. Identification of the molecular players involved in ovarian cancer dissemination can offer an approach to develop treatment strategies to improve clinical prognosis. Here, we identified mesothelin (MSLN) as a crucial protein in the multistep process of peritoneal dissemination of ovarian cancer. We demonstrated that MSLN is overexpressed in primary and matched peritoneal metastasis of high-grade serous carcinomas (HGSC). Using several genetically engineered ovarian cancer cell lines, resulting in loss or gain of function, we found that MSLN increased cell survival in suspension and invasion of tumor cells through the mesothelial cell layer in vitro. Intraperitoneal xenografts established with MSLN high ovarian cancer cell lines showed enhanced tumor burden and spread within the peritoneal cavity. These findings provide strong evidences that MSLN is a key player in ovarian cancer progression by triggering peritoneal dissemination and provide support for further clinical investigation of MSLN as a therapeutic target in HGSC.

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Primary heart neoplasms are rare occurring with an estimated incidence of 0.0017-0.19%. Myxoma is the most prevalent primary heart tumor. The right atrium is an unusual localization, occurring only in 15-20% of myxoma cases. We report a rare case of a massive right atrial myxoma causing tricuspid valve obstruction and presenting as syncope and exertional dyspnea. This case illustrates the influence of myxoma's size, position and mobility as well as patient's body posture and respiration to the development of signs and symptoms. Three-dimensional echocardiography proved useful in surgery planning, allowing a better definition of the tumor outline and attachment.

PURPOSE: To determine the risk of second primary neoplasms (SPNs) in subjects previously diagnosed with uveal melanoma (UM), including an analysis on whether radiotherapy is a risk factor to develop these SPNs.DESIGN: Retrospective cohort study. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) 9 database, we identified patients diagnosed with UM as their first malignancy between 1973 and 2011 (n [ 3976). We obtained standardized incidence ratios (SIR) and excess absolute risks of SPNs on patients with UM compared to a reference population. Multivariate Cox regression models were used to evaluate the effect of radiotherapy in SPN risk.RESULTS: Sixteen percent (n [ 641) of the patients developed SPNs during a median follow-up of 83 months (range, 1-463 months). This represented an 11% excess risk compared to the reference population, mainly owing to a significantly increased risk of skin melanomas (SIR [ 2.93, 95% CI: 2.23-3.78) and kidney tumors (SIR [ 1.91, 95% CI: 1.27-2.76), primarily in those diagnosed between 30 and 59 years of age. The occurrence of second UM was also increased (SIR [ 16.90, 95% CI: 9.00-28.90), which likely includes recurrences misclassified as a second cancer. Radiotherapy was performed in 39% (n [ 1538) of the patients. Multivariate analysis revealed that this treatment was not an independent risk factor for SPNs (hazard ratio [ 1.06, 95% CI: 0.88-1.26, P [ .54).CONCLUSIONS: Patients with UM presented an 11% higher risk of SPNs compared to the reference population. Radiotherapy does not seem to be a risk factor. SPNs should be considered in the surveillance of UM. (Am J Ophthalmol 2016;165:54-64. Ó 2016 Elsevier Inc. All rights reserved.) P UBLISHED DATA ON SURVIVAL OF UVEAL MELAnoma demonstrate that more than half of the patients are long-term survivors. At 5 and 10 years, the survival rates range between 68%-82% and 57%-62%, respectively.

Endometrial stromal sarcomas (ESSs) are rare tumors whose classification is still controversial. In this study, the authors studied 19 patients diagnosed with ESS at the Hospital S João, Porto, Portugal; reviewed their files and material; and performed immunohistochemical study for CD10, desmin, and smooth muscle actin markers, aiming to compare low-grade endometrial stromal sarcomas (LG-ESSs) and undifferentiated endometrial sarcomas (UESs) using the World Health Organization (WHO) classification. Twelve cases (63%) were classified as LG-ESS and 7 (37%) as UES. The median age at diagnosis was 49 years, and women with LG-ESS tended to be younger than those with UES. Most cases (7/11) had a previous echographic diagnosis of leiomyoma. A biopsy or curettage was performed in 6 cases, providing a definitive diagnosis of malignancy in 4. Frozen section was performed in 4 patients. The majority (63%) of patients were FIGO stage I. Twelve (63%) cases showed diffuse or focal expression of CD10. Desmin and smooth muscle actin expression was focal in 4 (21%) tumors. Patients with LG-ESS had a significant better overall survival than those with UES (P = .026). Mitotic count had no prognostic significance. Our data emphasize the clinical importance of the WHO classification in ESS. It is of utmost importance to establish a proper classification to increase the consistency of data that may be useful for improving clinical and therapeutic management of patients with ESS.

This review focuses on the most common diagnostic pitfalls and helpful morphologic and immunohistochemical markers in the differential diagnosis between the different subtypes of endometrial carcinomas, including: (1) endometrioid versus serous glandular carcinoma, (2) papillary endometrioid (not otherwise specified, villoglandular and nonvillous variants) versus serous carcinoma, (3) endometrioid carcinoma with spindle cells, hyalinization, and heterologous components versus malignant mixed müllerian tumor, (4) high-grade endometrioid versus serous carcinoma, (5) high-grade endometrioid carcinoma versus dedifferentiated or undifferentiated carcinoma, (6) endometrioid carcinoma with clear cells versus clear cell carcinoma, (7) clear cell versus serous carcinoma, (8) undifferentiated versus neuroendocrine carcinoma, (9) carcinoma of mixed cell types versus carcinoma with ambiguous features or variant morphology, (10) Lynch syndrome-related endometrial carcinomas, (11) high-grade or undifferentiated carcinoma versus nonepithelial uterine tumors. As carcinomas in the endometrium are not always primary, this review also discusses the differential diagnosis between endometrial carcinomas and other gynecological malignancies such as endocervical (glandular) and ovarian/peritoneal serous carcinoma, as well as with extra-gynecologic metastases (mainly breast and colon).

AimsLymphovascular space invasion (LVSI) in endometrial cancer (EC) is an important prognostic variable impacting on a patient's individual recurrence risk and adjuvant treatment recommendations. Recent work has shown that grading the extent of LVSI further improves its prognostic strength in patients with stage I endometrioid EC. Despite this, there is little information on the reproducibility of LVSI assessment in EC. Therefore, we designed a study to evaluate interobserver agreement in discriminating true LVSI from LVSI mimics (Phase I) and reproducibility of grading extent of LVSI (Phase II).Methods and resultsScanned haematoxylin and eosin (H&E) slides of endometrioid EC (EEC) with a predefined possible LVSI focus were hosted on a website and assessed by a panel of six European gynaecological pathologists. In Phase I, 48 H&E slides were included for LVSI assessment and in Phase II, 42 H&E slides for LVSI grading. Each observer was instructed to apply the criteria for LVSI used in daily practice. The degree of agreement was measured using the two‐way absolute agreement average‐measures intraclass correlation coefficient (ICC). Reproducibility of LVSI assessment (ICC = 0.64, P < 0.001) and LVSI grading (ICC = 0.62, P < 0.001) in EEC was substantial among the observers.ConclusionsGiven the good reproducibility of LVSI, this study further supports the important role of LVSI in decision algorithms for adjuvant treatment.