Ovarian serous carcinoma (OSC) is a fatal gynecologic malignancy usually presenting with bilateral localization and malignant peritoneal effusion. Programmed cell death 4 (PDCD4) is a tumor suppressor gene whose expression is directly controlled by microRNA-21 (miR-21). Exosomes are small cell-derived vesicles that participate in intercellular communication, delivering their cargo of molecules to specific cells. Exosomes are involved in several physiological and pathological processes including oncogenesis, immunomodulation, angiogenesis, and metastasis. The current study analyzed the expression of PDCD4 and miR-21 in resected OSC specimens and in cells and exosomes from OSC peritoneal effusions. PDCD4 was immunohistochemically examined in 14 normal ovaries, 14 serous cystadenoma (CA), and 14 OSC cases. Quantitative reverse transcriptase-polymerase chain reaction analysis of PDCD4 and miR-21 expression was performed in CA and OSC cases and in cells and exosomes obtained from 10 OSC and 10 nonneoplastic peritoneal effusions. miR-21 was also evaluated by in situ hybridization. Immunohistochemistry demonstrated a gradual PDCD4 loss from normal ovaries to CA and OSC specimens. Quantitative reverse transcriptase-polymerase chain reaction displayed higher PDCD4 messenger RNA levels in CA specimens compared with OSC cases and highlighted miR-21 overexpression in OSC specimens. In situ hybridization detected miR-21 only in OSC cells. This PDCD4 and miR-21 inverse expression was also noted in cells and exosomes from OSC peritoneal effusions compared with nonneoplastic effusions. PDCD4 and miR-21 are involved in OSC oncogenesis. The transfer of miR-21 by exosomes could promote oncogenic transformation in target cells distant from the primary tumor without direct colonization by cancer cells and could be used as a diagnostic tool

Purpose:To analyze immunohistochemically morules in endometrioid lesions to show that CD10 is a sensitive marker for morular metaplasia. Experimental Design: Immunohistochemical analysis of 53 instances of morular metaplasia comprising 1 cyclic endometrium and 52 endometrioid lesions associated with focal glandular complexity corresponding to 9 polyps, 4 atypical polypoid adenomyomas, 24 complex endometrial hyperplasias (18 with and 6 without atypia), 12 grade 1 endometrioid adenocarcinomas in early clinical stages of both uterus and ovary, and three ovarian adenofibromas. Immunohistochemistry in paraffin sections was done for CD10, h-catenin, estrogen and progesterone receptors, and cytokeratins 5-6, 7, 8, 13, 18, 19, 20, and 34h-E12. Results: Morules were negative for estrogen and progesterone receptors and had h-cateninp ositive nuclei. Cytokeratins 8, 18, 19 were positive; cytokeratins 7 and 20 were negative; and cytokeratins 5-6, 13, and 34h-E12 were weakly positive. All cases revealed strongly positive membranous CD10 staining in morules, which was absent in glands. CD10 positivity allowed easy identification of morules at low power in various types of surgical specimens and in curettings. CD10 also highlighted early morular metaplasia in glandular epithelium. In cases associated with squamous, keratinizing metaplasia, CD10 discriminated between both types of metaplasia. Conclusions: CD10 staining represents a useful marker of morules in endometrioid neoplasms of the female genital tract, permitting identification of lesions usually associated with an attenuated malignancy. Considering the immunohistochemical and genetic similarities of morules in tumors of different organs, it is likely that this marker may be also useful to diagnose morular metaplasia in similar neoplasms of extragenital locations.Morules (1) are nodular structures found in endometrial-type glands formed by a peculiar metaplastic non-keratinizing squamoid epithelium (2). Morphologically similar structures have also been described in neoplastic lesions in other anatomic sites, such as thyroid (3), lung (4, 5), stomach (6), pancreas (7), and colon (8).In both eutopic and ectopic endometrioid tissues, morules are almost invariably associated with the glandular architectural complexity of premalignant and low-grade glandular malignant lesions but are absent in high-grade ones. Thus, it can be said that the presence of morules in the endometrium relates well with an attenuated malignancy.This study deals with the immunohistochemical findings in a series of 53 cases of morular metaplasia from both uterus and ovary, showing for the first time that CD10 staining is a marker of morules, allowing its easy identification in various endometrioid lesions. Materials and MethodsA total of 53 cases of endometrioid morular metaplasia were collected from the files of the

These data show a lack of toxicity of T. monococcum gliadin in an in vitro organ culture system, suggesting new dietary opportunities for celiac patients.

Glucose transporter 4 (GLUT4) seems to be involved in the mechanism of insulin resistance in polycystic ovary syndrome (PCOS) patients (PCOSs) in both muscular and adipose tissue. The observation that insulin stimulates glucose oxidation in endometrial cells led us to investigate the presence of GLUT4 in this tissue and whether a defect of GLUT4 is present at the endometrial level in PCOSs. We also investigated whether body weight influences GLUT4 expression in this syndrome. GLUT4 mRNA content was examined by real-time quantitative RT-PCR and immunostaining reaction in the endometrial tissue of nine normal subjects, nine lean and eight obese hyperinsulinemic (h-INS), and eight lean and 10 obese normoinsulinemic (n-INS) PCOSs. GLUT4 mRNA and its positive immunostaining reaction were present in epithelial cell level in the endometrium of both normal and PCOS subjects. Significantly higher levels of GLUT4 were observed in normal and lean n-INS PCOSs in comparison with other groups. In both n-INS and h-INS obese PCOSs, GLUT4 was significantly lower than in lean subjects. However, obese n-INS and lean h-INS PCOSs showed a similar low GLUT4 expression, whereas obese h-INS PCOSs showed the lowest expression when compared with other groups. In conclusion, our data demonstrate that GLUT4 is present in the endometrium of normal and PCOS subjects and that hyperinsulinism and obesity seem to have a negative effect on endometrial GLUT4 expression in PCOS.

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