Abstract. Changes in the expression of the mismatch repair (MMR) genes hMSH2, hMLH1, hMSH6 and hPMS2 reflect dysfunction of the DNA repair system that may allow the malignant transformation of tissue cells. The aim of the present study was to address the mRNA expression profiles of the mismatch DNA repair system in cancerous and precancerous urothelium. This is the first study to quantify MMR mRNA expression by applying quantitative real-time PCR (qPCR) and translate the results to mRNA phenotypic profiles (r, reduced; R, regular or elevated) in bladder tumors [24 urothelial cell carcinomas (UCCs) and 1 papillary urothelial neoplasm of low malignant potential (PUNLMP)] paired with their adjacent normal tissues (ANTs). Genetic instability analysis was applied at polymorphic sites distal or close to the hMSH2 and hMLH1 locus. Presenting our data, reduced hMSH2, hMSH6 and hPMS2 mRNA expression profiles were observed in cancerous and precancerous urothelia. Significantly, the ANTs of UCCs revealed the highest percentages of reduced hMSH2 (r 2 ), hMSH6 (r 6 ) and hPMS2 (p 2 ) mRNA phenotypes relative to their tumors (P<0.03). In particular, combined r 2 r 6 (P<0.02) presented a greater difference between ANTs of low-grade UCCs vs. their tumors compared with ANTs of high-grade UCCs (P= 0.000). Reduced hMLH1 (r 1 ) phenotype was not expressed in precancerous or cancerous urothelia. The hMSH6 mRNA was the most changed in UCCs (47.8%), while hMSH2, hMLH1 and hPMS2 showed overexpression (47.8, 35 and 30%, respectively) that was associated with gender and histological tumor grading or staging. Genetic instability was rare in polymorphic regions distal to hMLH1. Our data reveal a previously unrecognized hMSH2 and hMSH6 mRNA combined phenotype (r 2 r 6 ) correlated with a precancerous urothelium and show that hMLH1 is transcriptionally activated in precancerous or cancerous urothelium. In the present study, it is demonstrated that reduction of hMSH6 mRNA is a frequent event in bladder tumorigenesis and reflects a common mechanism of suppression with hMSH2, while alterations of hMSH2 or hMLH1 mRNA expression in UCCs does not correlate with the allelic imbalance of polymorphic regions harboring the genes. IntroductionThe most common histological type of bladder cancer is urothelial cell carcinoma (UCC) or transitional cell carcinoma (TCC). Papillary urothelial neoplasm of low malignant potential (PUNLMP) may also arise from urothelium of bladder (1,2). The urothelium of a patient with a bladder cancer is at risk as the cancer often recurrs in the urinary bladder following treatment (1,3). Numerous genetic and epigenetic factors have been implicated in the carcinogenesis of the urinary bladder that involved in its mutator phenotype (4-7). The DNA repair mechanism is essential to prevent DNA mutations that may be lethal for cells (8). Mismatch repair (MMR) genes encode a number of DNA repair enzymes that cooperate to recognize and repair DNA mismatches (8,9). These enzymes act as complexes. A crucial complex that recognizes base...

We present a case of dermatomyositis together with polycythemia as initial manifestations of a particularly rare type of prostate cancer. A 69-year-old man was hospitalized for facial erythema and symptoms of fatigue. Physical evaluation, serum creatinine phosphokinase and electromyography were consistent with dermatomyositis. In parallel, the hemoglobin level was 18.5 g/dL, serum erythropoietin levels were low normal and no JAK2 mutation was found. Given a strong suspicion of a paraneoplastic syndrome the patient underwent abdominal computed tomography revealing a prostate mass, enlarged iliac lymph nodes and a fracture of L1 due to metastasis. The unusual paraneoplastic manifestations prompted a more thorough immunohistologic examination of the needle biopsy specimen taken from the prostate, which led to the diagnosis of large cell neuroendocrine prostate carcinoma. It is a most rare type of prostate cancer, carrying a poor prognosis. To our knowledge, this is the first case in the literature associating a neuroendocrine cancer of the prostate with dermatomyositis.

Objective. The most appropriate technique for excising the distal ureter and bladder cuff during laparoscopic nephroureterectomy is still debated. We report our experience with a pure laparoscopic transvesical method that duplicates the long-standing open transvesical approach. Materials and Methods. Seven men and three women diagnosed with upper tract transitional cell carcinoma were treated with this procedure. Three intravesical ports were inserted, and pneumovesicum was established at 12 mmHg. Transvesical laparoscopic circumferential detachment of the bladder cuff and en bloc mobilization of the last centimeters of the distal ureter were performed, followed by the closure of the bladder defect. Subsequently, a nephrectomy was performed either laparoscopically or using an open flank approach. Results. The median age was 68.5 years. The procedure was completed uneventfully in all cases. The median operating time for distal ureter excision was 82.5 minutes (range 55–120). No complications directly related to the pneumovesicum method were recorded. The median follow-up period was 31 months (range 12–55). During the follow-up period, two patients (20%) died from the disease, and a bladder tumor developed in three cases (30%). Conclusion. The laparoscopic transvesical resection of the en bloc bladder cuff and distal ureter is a reliable, effective, and oncologically safe technique, at least in the midterm.