Expression and polymorphism of micro-RNA according to body mass index and breast cancer presentation in Tunisian patients.

Micro-RNAs (miRs) constitute a class of small noncoding RNAs implicated in the regulation of gene expression by binding to target mRNAs. A miR can target several mRNAs, being involved in different biologic processes and pathologies. This pleiotropic function might explain the link between diseases co-occurrence. Epigenetic origin of the link between obesity and breast cancer (BC) is investigated in a cohort of Tunisian patients, focusing on polymorphism at germline level (miR-146a) and on expression in mammary tumors (miR-21, miR-146a, and miR-34a), according to body mass index (BMI) and clinico-pathologic features. The measure of miR expression in 60 mammary tumors was realized using quantitative RT-PCR. Study of rs 2910164 in miR-146a was performed by PCR and direct sequencing using blood DNA of 83 affected women and 50 unrelated subjects from Great Tunis. MiR-21, miR-146a, and miR-34a have been quantified in breast tumor according to BMI. MiR-21 is significantly more expressed in tumors of obese women comparatively to nonobese patients. On the contrary, miR-34a is decreased in tumors of obese women. Moreover, in obese BC patients, a significant increase in both miR-21 and miR-146a expression is revealed in cases with lymph node metastasis. The polymorphism at rs 2910164 (miR-146a) locus was not shown as a risk factor for BC. However the mutant CC genotype was revealed to be associated with a risk for bad outcome of the disease. Chronic inflammation in obese women would be linked to aggressive breast tumors via induction of oncomiRs overexpression and decrease of tumor suppressor miRs.

Single-cell genetic analysis validates cytopathological identification of circulating cancer cells in patients with clear cell renal cell carcinoma.

CONTEXT: Circulating Rare Cells (CRC) are non-haematological cells circulating in blood. They include Circulating Cancer Cells (CCC) and cells with uncertain malignant features (CRC-UMF) according to cytomorphology. Clear cell renal cell carcinomas frequently bear a mutated Von Hippel-Lindau (VHL) gene. AIM: To match blind genetic analysis of CRC and tumor samples with CRC cytopathological diagnosis. RESULTS: 29/30 patients harboured CRC (20 harboured CCC, 29 CRC-UMF) and 25/29 patients carried VHL mutations in their tumour. 205 single CRC (64 CCC, 141 CRC-UMF) provided genetic data. 57/57 CCC and 104/125 CRC-UMF from the 25 patients with VHL-mutated tumor carried the same VHL mutation detected in the tumor. Seven CCC and 16 CRC-UMF did not carry VHL mutations but were found in patients with wild-type VHL tumor tissue. CONCLUSIONS: All the CCC and 83,2% (104/125) of the CRC-UMF were found to carry the same VHL mutation identified in the corresponding tumorous tissue, validating cytopathological identification of CCC in patients with clear cell renal cell carcinoma. METHODS: The blood of 30 patients with clear cell renal cell carcinoma was treated by ISET® for CRC isolation, cytopathology and single-cell VHL mutations analysis, performed blindly and compared to VHL mutations of corresponding tumor tissues and leukocytes.

[Hypercalcemia related to PTH-rP revealing malignant hepatic epithelioid hemangioendothelioma]. / Une hypercalcémie humorale maligne révélant un hémangioendothéliome épithélioïde du foie.

Hypercalcemia caused by tumor production of PTH-rp occurs most often in cases of squamous cell carcinoma of the lung, aerodigestive tract cancer, gynecological cancer and lymphoma. We report an exceptional case of PTH-rp related to a hepatic hemangioendothelioma. A 70 years-old male admitted for deterioration of the general state. The laboratory investigations revealed hypercalcemia, related to tumor production of PTH-rp. Imaging revealed tumoral hepatic lesions. Histopathological study and immunohistochemistry showed diffuse response for CD31 marker, CK20 (+) with CK7 (-) and hepatocyt antigen (-). The diagnosis of PTH-rp related to hepatic hemangioendothelioma was make. The patient died with recurrence of fatal hypercalcemia. Management of patients presenting with humoral hypercalcemia includes a vigorous search for tumor lesions. Elevated PTH-rp can be a bad prognostic factor. In front of tumoral liver lesions, a hepatic epithelioid hemangioendothelioma must be considered. Immunohistochemistry is necessary to make diagnosis.

Wild-type genotypes of BRCA1 gene SNPs combined with micro-RNA over-expression in mammary tissue leading to familial breast cancer with an increased risk of distant metastases' occurrence.

Germ line deleterious mutations of BRCA1 gene are not the unique factor that could inactivate BRCA1 protein which leads to familial breast cancer onset with distant metastases' occurrence. The present research explores the role that could be assigned to BRCA1 SNPs to inactivate BRCA1 protein and therefore to the occurrence of familial breast cancer with an increased risk of distant metastases' occurrence. The presence or the absence of BRCA1 protein was first analyzed by applying the immunohistochemistry technique to the tumors with sporadic and familial breast cancer. Then, a case-control study was conducted including 40 patients with familial breast cancer, 46 ones with sporadic breast cancer and 34 healthy controls based on the genotyping of nine BRCA1 SNPs (c.442.58delT, c.2082C>T, c.2311T>C, c.2612C>T, c.3113A>G, c.3119G>A, c.3548A>G, c.4308T>C and 4837A>G) via direct sequencing. Finally, the functional role that could be assigned to these SNPs was focused upon. miRbase site was used as a bioinformatics tool to predict potential micro-RNAs (miRs) targeting SNPs that are associated with familial breast cancer according to the results of this research. These predicted miRs were confirmed by Q-PCR analysis and correlated with BRCA1 protein expression among patients along with potential distant metastases. Clinical outcome showed that distant metastasis concerned 45 % of familial breast cancer patients and 19.5 % with sporadic breast cancer. Analysis of BRCA1 protein expression revealed a negative staining among 46.6 % of familial breast cancer patients and only 16.6 % within sporadic breast cancer ones. The association of four variants was identified within BRCA1 gene (c.442.58 delT, c.2311T>C, c.2612C>T and c.4308T>C) to familial breast cancer across their wild genotypes. miR-1179 was selected as potential miR that targets the region of BRCA1 mRNA containing the c.2311T>C variant within the TT genotype. The expression of miR-1179 was significantly associated with familial breast cancer patients without BRCA1 deleterious mutations compared to those with sporadic breast cancer according to TT genotype along with BRCA1 negative staining and according to the occurrence of distant metastases. Combination between TT genotype of c.2311T>C and miR-1179 over-expression could generate a lack of BRCA1 protein leading to a high risk of familial breast cancer with distant metastases.

Aurora A overexpression and pVHL reduced expression are correlated with a bad kidney cancer prognosis.

We investigate the expression and localization of the tumor suppressor protein pVHL as well as the oncoprotein Aurora A kinase in kidney cancer. Both Aurora A kinase and pVHL protein status were evaluated using immunohistochemistry. The Aurora A expression is correlated with the Fuhrman grade and the TNM stage, while the pVHL expression is correlated with the capsule rupture and the TNM stage. Aurora A kinase expression increases in malignant tissue comparing to the non-malignant one. And there is a decrease in pVHL expression from the adjacent healthy tissues to the tumor`s ones. The two kinds of opposite tumor profiles display significant distribution difference according to TNM stages. It could be proposed that the absence of Aurora A protein associated with a strong expression of pVHL in clear cells kidney carcinoma are of good prognosis for the disease.

Malignant solitary fibrous tumor in the extremity: Cytopathologic findings.

Malignant solitary fibrous tumor (SFT) is an extremely rare neoplasm. There are only rare published accounts of the cytopathologic features of this tumor. We report a case of a 59-year-old woman presented with a 10-year history of a right thigh mass. A preoperative fine needle aspiration (FNA) was performed. Smears were hypercellular, with cohesive and crowded tissue fragments, haphazard cell arrangements and many single cells. The tumor cells were polymorphous, plump spindled or round with often indented or bare nuclei. A differential diagnosis of low grade sarcoma was favored. The diagnosis of malignant SFT is extremely difficult on FNA and must be included in the differential diagnosis of spindle cell neoplasms.

Cotyledonoid dissecting leiomyoma of the uterus associated with endosalpingiosis.

Cotyledonoid dissecting leiomyoma (CDL) may create a diagnostic challenge. A 47-year-old woman underwent laparotomy for a large pelvic mass associated to vaginal bleeding. During operation, a bulky deep red mass protruding from the uterus and projecting into the pelvic cavity was discovered. Allowing to sarcoma- like appearance, a total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed with removal of the pelvic tumor extension. The diagnosis of cotyledonoid dissecting leiomyoma of the uterus associated with endosalpingiosis was performed. To the best of our knowledge, this association has never been encountered in the English literature.

[Cholestasis caused by a choledochal botryoid rhabdomyosarcoma in a 22-month-old boy]. / Une choléstase causée par un rhabdomyosarcome botryoïde du cholédoque chez un nourrisson de 22 mois.

Botrioid rhabdomyosarcoma of the extrahepatic bile ducts is a rare cause of jaundice in children. It has a very poor prognosis and is rarely diagnosed preoperatively. We report a choledochal botrioid rhabdomyosarcoma in a 22-month-old boy who developed an obstructive jaundice. Radiographic explorations suggested cystic lymphangioma. The gallbladder, the cystic duct, the common bile duct and the pancreatic head were resected. The diagnosis was made on pathological examination; adjuvant chemotherapy followed. The patient was disease free 20 months following treatment.

[Retroperitoneal well-differentiated inflammatory liposarcoma]. / Liposarcome bien différencié inflammatoire rétropéritonéal.

Inflammatory liposarcoma represents a rare variant of well-differentiated liposarcoma in which a chronic inflammatory infiltrate predominates simulating the appearance of malignant lymphoma and other nonneoplastic lesions. A case of this lesion occurring in the retroperitoneum was described in 43-year-old man. The differential diagnosis, especially from lymphoma and non neoplastic lesions such as inflammatory myofibroblastic tumor and Castelman disease are discussed.

[Atypical mesoblastic nephroma: histopathological entity or specific anatomoclinical form?]. / Le néphrome mésoblastique cellulaire ou atypique: entité histopathologique ou forme anatomo-clinique particulière?

Atypical mesoblastic nephroma is a rare kidney tumor mostly which occurred in early infancy. We describe two cases of atypical mesoblastic nephroma diagnosed in infants aged respectively 2 and 3 months. The tumors were completely removed and surgical margins were histologically free of disease. The two patients are well 14 and 9 months after surgery. Microscopically, the tumor was characterized by a densely cellular proliferation, high mitotic levels, cystic degeneration and necrosis. In the literature, the prognostic is good in patients aged fewer than 3 months and in cases in which the surgical removal was complete.