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Among the four endometrial cancer (EC) TCGA molecular groups, the MSI/hypermutated group represents an important percentage of tumors (30%), including different histotypes, and generally confers an intermediate prognosis for affected women, also providing new immunotherapeutic strategies. Immunohistochemistry for MMR proteins (MLH1, MSH2, MSH6 and PMS2) has become the optimal diagnostic MSI surrogate worldwide. This review aims to provide state-of-the-art knowledge on MMR deficiency/MSI in EC and to clarify the pathological assessment, interpretation pitfalls and reporting of MMR status.

This study investigated whether radiomic features extracted from pretreatment [18F]FDG PET could improve the prediction of both histopathologic tumor response and survival in patients with locally advanced cervical cancer (LACC) treated with neoadjuvant chemoradiotherapy followed by surgery compared with conventional PET parameters and histopathologic features. Methods: The medical records of all consecutive patients with LACC referred between July 2010 and July 2016 were reviewed. [18F]FDG PET/CT was performed before neoadjuvant chemoradiotherapy. Radiomic features were extracted from the primary tumor volumes delineated semiautomatically on the PET images and reduced by factor analysis. A receiver-operating-characteristic analysis was performed, and conventional and radiomic features were dichotomized with Liu's method according to pathologic response (pR) and cancer-specific death. According to the study protocol, only areas under the curve of more than 0.70 were selected for further analysis, including logistic regression analysis for response reduction and Cox regression analysis for survival prediction. Results: A total of 195 patients fulfilled the inclusion criteria. At pathologic evaluation after surgery, 131 patients (67.2%) had no or microscopic (≤3 mm) residual tumor (pR0 or pR1, respectively); 64 patients (32.8%) had macroscopic residual tumor (>3 mm, pR2). With a median follow-up of 76.0 mo (95% CI, 70.7-78.7 mo), 31.3% of patients had recurrence or progression and 20.0% died of the disease. Among conventional PET parameters, SUVmean significantly differed between pathologic responders and nonresponders. Among radiomic features, 1 shape and 3 textural features significantly differed between pathologic responders and nonresponders. Three radiomic features significantly differed between presence and absence of recurrence or progression and between presence and absence of cancer-specific death. Areas under the curve were less than 0.70 for all paramete

Herein, we present a clinicopathological and molecular analysis of four cases of endometrial carcinoma (EC) diffusely exhibiting dyshesive cells with wide eosinophilic and vacuolated cytoplasm (histiocyte-like tumor cells, HLTCs). We compared these HLTCs to similar cells found in microcystic, elongated and fragmented (MELF) pattern (n = 20) or after neoadjuvant chemotherapy (NAC) (n = 5). The four cases were endometrioid, serous, clear cell, and gastric-type; all were at FIGO stage >= III. HLTCs showed an epithelial Mullerian phenotype and at least focal CK20, HNF1 beta, and CK5/6 expression, with aberrant e-cadherin and beta-catenin expression; two cases were MMR-deficient, and one was p53-abnormal; all were POLE wild type. MELF-associated and NAC-associated HLTCs showed similar morphological/immunophenotypical features. However, MELF-associated HLTCs were mainly intraglandular and inflammation-associated, did not form a distinct tumor component, and showed no relationship with lymph node metastases. In conclusion, different histotypes of EC may show a prominent HLTC component, which shows peculiar morphological/immunophenotypical features and appears associated with aggressive behavior.

OBJECTIVE: To describe the clinical and ultrasound characteristics of uterine sarcomas. METHODS: This is a retrospective multicenter study. From the databases of 13 ultrasound centers, we identified patients with a histological diagnosis of uterine sarcoma with available ultrasound reports and ultrasound images who had undergone preoperative ultrasound examination between 1996 and 2016. As a first step, each author collected information from the original ultrasound reports on predefined ultrasound features of the tumors from his/her own center and by checking the ultrasound images to find information on variables not described in the original report. As a second step, 16 ultrasound examiners reviewed electronic ultrasound images in a consensus meeting and described them using a predetermined terminology. RESULTS: We identified 116 patients with a leiomyosarcoma, 48 with endometrial stromal sarcoma, and 31 with undifferentiated endometrial sarcoma. Median age of the patients was 56 (range, 26-86) years. Most patients were symptomatic at diagnosis (164/183, 89.6%), the most frequent presenting symptom being abnormal vaginal bleeding (91/183, 49.7%). Patients with endometrial stromal sarcoma were younger than patients with leiomyosarcoma or undifferentiated endometrial sarcoma (median age 46 years vs 57 vs 60). The results of the first and second step of analysis were similar. According to the assessment by the original ultrasound examiners, the median largest tumor diameter was 91 (range 7-321) mm. Visible normal myometrium was reported in 149/195 (76.4%) cases, and 80% (156/195) of lesions were solitary. Most sarcomas were solid masses (>80% solid tissue) (155/195, 79.5%) and most manifested inhomogeneous echogenicity of the solid tissue (151/195, 77.4%), one sarcoma was multicystic without solid components. Cystic areas were described in 87/195 (44.6%) tumors and most cyst cavities had irregular walls (67/87, 77.0%). Internal shadowing was observed in 42/192 (21.

BACKGROUND: Activating mutations in the valine-to-glutamic acid substitution at position 600 of the v-raf murine sarcoma viral oncogene homolog B1 (BRAF-1) gene are detected frequently in patients with papillary thyroid carcinoma (PTC). These mutations have been identified in approximately 29% to 69% of PTCs and in >80% of PTCs of the tall cell variant, whereas they have not been detected in benign lesions or in the majority of those (80%) with the follicular variant of PTC. The objective of the current study was to evaluate the role of liquid-based cytology (LBC) for the detection of BRAF mutations in the outcome of patients who have thyroid PTC measuring ≤1 cm and, hence, in guiding their clinical and surgical management. METHODS: From October 2010 through June 2011, 230 consecutive cases were diagnosed as positive for malignancy on fine-needle aspiration cytology processed by LBC. Of these, 73 PTCs ≤1 cm underwent BRAF mutational analysis. The aspirated material was processed using an LBC technique. After DNA extraction of the residual material, BRAF mutation analysis was performed using a direct sequencing method. RESULTS: Fifty of 73 patients (68.5%) underwent surgery, and 34 of those patients (68%) had tumors that expressed a BRAF mutation (31 PTCs, including 11 tall cell variants and 3 follicular-variant PTCs). A significant association between BRAF mutation and bilaterality of cancer was observed (odds ratio, 0.077; P = .0007). BRAF mutation was associated significantly with lymph node involvement (odds ratio, 19; P = .0007) but not with extracapsular infiltration (odds ratio, 0.298; P = .179). CONCLUSIONS: The current results indicated that BRAF gene mutations can be identified successfully on LBC material and using other cytologic methods with high reproducibility, feasibility, and informative results. The presence of a BRAF mutation may preoperatively predict the behavior of microscopic PTC, suggesting a more aggressive surgical approach. Cancer (Cancer C

Only two cases of recurrence of heterologous carcinosarcoma from adenocarcinoma of the ovary have been documented in the published literature. We report a case of serous ovarian carcinoma recurring as a heterologous carcinosarcoma. The immunohistochemical analysis of several biological parameters in primary ovarian adenocarcinoma and recurrent carcinosarcoma has been also performed.

PURPOSE: To assess magnetic resonance (MR) imaging in depicting the depth of myometrial infiltration, cervical invasion, and presence of enlarged lymph nodes in patients with endometrial adenocarcinoma compared with surgicopathologic findings. MATERIALS AND METHODS: Thirty-seven consecutive patients with endometrial carcinoma were included in this prospective study. All patients underwent MR imaging and surgery. Qualitative image analysis included the depth of myometrial infiltration, infiltration of the uterine cervix, and presence of enlarged lymph nodes. Quantitative image analysis included tumor and myometrium contrast-to-noise ratios during different phases of dynamic imaging. MR imaging findings were compared with surgicopathologic findings. Sensitivity, specificity, diagnostic accuracy, and positive and negative predictive values of MR imaging in depicting myometrial and cervical infiltration and in lymph node assessment were calculated. RESULTS: Respective sensitivity, specificity, diagnostic accuracy, and positive and negative predictive values in assessing myometrial infiltration were 87%, 91%, 89%, 87%, and 91%; those for cervical infiltration, 80%, 96%, 92%, 89%, and 93%; and those for lymph node assessment, 50%, 95%, 90%, 50%, and 95%. There was significant agreement between MR imaging and surgicopathologic findings in assessment of myometrial invasion (P <.001). Myometrial and cervical invasion and lymph node enlargement were correctly assessed with MR imaging in 28 (76%) of 37 patients. Quantitative analysis showed a significant improvement in tumor and myometrium contrast-to-noise ratios during the equilibrium phase compared with the arterial and precontrast phases (P <.001). CONCLUSION: MR imaging coupled with contrast material-enhanced dynamic MR imaging is highly accurate in local-regional staging of endometrial carcinoma; more challenging is the assessment of pelvic and lumboaortic lymph nodes.

ZEB2 is a key factor in epithelial-mesenchymal transition (EMT), a program controlling cell migration in embryonic development and adult tissue homeostasis. We demonstrated a role of ZEB2 in migration and anchorage-independent cell growth in ovarian cancer, as shown by ZEB2 silencing. We found that the RNA-binding protein HuR bound the 3'UTR of ZEB2 mRNA, acting as a positive regulator of ZEB2 protein expression. In Hey ovarian cell line, HuR silencing decreased ZEB2 and ZEB1 nuclear expression and impaired migration. In hypoglycemic conditions ZEB2 expression decreased, along with ZEB1, vimentin and cytoplasmic HuR, and a reduced cellular migration ability was observed. Analysis of ZEB2 and HuR expression in ovarian cancers revealed that nuclear ZEB2 is localized in tumor leading edge and co-localizes with cytoplasmic HuR. In a series of 143 ovarian cancer patients high expression of ZEB2 mRNA significantly correlated with a poor prognosis in term of both overall survival and progression- free survival. Moreover, at immunohistochemical evaluation, we found that prognostic significance of ZEB2 protein relies on its nuclear expression and co-localization with cytoplasmic HuR. In conclusion our findings indicated that nuclear ZEB2 may enhance progression of EMT transition and acquisition of an aggressive phenotype in ovarian cancer.