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Detection of Bladder Cancer from the Urine using Fluorescence in situ Hybridization Technique

The authors report on their first experiences with the UroVysion fluorescencein situ hybridization (FISH) kit developed for the detection of bladder cancer. This new non-invasive diagnostic application of the FISH technique in the field of urology was elaborated to replace cystoscopy. The special urine examination method detects genetic alterations of the urothelial cells found in the urine, using fluorescent directlabeled DNA probes binding to the peri-centromeric regions of chromosomes 3, 7 and 17 as well as on the 9p21 locus. We aimed to evaluate the utility of UroVysion test in the light of the histological diagnosis. Urine samples from 43 bladder cancer patients and 12 patients with no or benign alterations were studied using a new application of FISH technique: the UroVysion reagent kit. The obtained FISH results were compared with the histological findings of the transurethral surgical resection specimens. The study rated the specificity and sensitivity of the technique 100% and 87%, respectively. Therefore, the technique could well fit into the diagnostic process of bladder carcinomas. Statistical analyses showed significant correlation between tumor progression and the severity of the genetic alterations detected by this FISH technique. Furthermore, positive correlation was found between tumor grade and the proportion of tumor cells showing genetic abnormality. The noninvasiveness, the robustness of evaluation and the high specificity/sensitivity are all in favor of this technique. The disadvantages are the higher costs of the technical background and the required future clinical studies to determine whether this technique can replace cystoscopy.

Tricellulin expression in normal and neoplastic human pancreas

Korompay A, Borka K, Lotz G, Somorácz Á, Törzsök P, Erdélyi‐Belle B, Kenessey I, Baranyai Z, Zsoldos F, Kupcsulik P, Bodoky G, Schaff Z & Kiss A

Expression of Claudins and Their Prognostic Significance in Noninvasive Urothelial Neoplasms of the Human Urinary Bladder

The members of the claudin family are major integral transmembrane protein constituents of tight junctions. Normal and neoplastic tissues can be characterized by unique qualitative and quantitative distribution of claudin subtypes, which may be related to clinicopathological features. Differential diagnosis and prognosis of nonmuscle invasive tumor entities of urinary bladder epithelium are often challenging. The aim was to investigate the expression profile of claudins in inverted urothelial papillomas (IUPs), urothelial papillomas (UPs), papillary urothelial neoplasms of low malignant potential (PUNLMPs), and intraepithelial (Ta), low-grade urothelial cell carcinomas (LG-UCCs) in order to reveal potential prognostic and differential diagnostic values of certain claudins. Claudin-1, -2, -4, and -7 protein expressions detected by immunohistochemistry and clinical data were analyzed in 15 IUPs, 20 UPs, 20 PUNLMPs, and 20 LG-UCCs. UPs, PUNLMPs, and LG-UCCs showed significantly decreased claudin-1 expression in comparison to IUPs. LG-UCCs expressing claudin-4 over the median were associated with significantly shorter recurrence-free survival. PUNLMPs expressing claudin-1 over the median revealed significantly longer recurrence-free survival. High claudin-1 protein expression might help to differentiate IUP from UPs, PUNLMPs, and LG-UCCs. High claudin-4 expression may determine an unfavorable clinical course of LG-UCCs, while high claudin-1 expression in PUNLMP was associated with markedly better clinical outcome.

Molecular Characteristics of Fibrolamellar Hepatocellular Carcinoma

Fibrolamellar hepatocellular carcinoma (FLC) occurs in non-cirrhotic liver and the etiopathogenesis is still obscure. Both hepatocellular and cholangiocellular markers are expressed in the tumor, however, molecular alterations and altered pathways playing role in the tumor pathogenesis are not clearly identified. The purpose of the present study was to compare the expression level of EGFR, syndecan-1 and ß-catenin in FLC, conventional hepatocellular carcinoma (cHCC) and cholangiocellular carcinoma (CCC) and to investigate the possibility of mutation both in EGFR and K-RAS. Eight FLCs were compared with 7 cHCCs, 7 CCCs and 5 normal liver samples. Cytokeratins 7, 8, 18, 19, HepPar1 (HSA), EGFR, syndecan-1 (CD138) and ß-catenin were detected by immunohistochemistry. In addition EGFR, ß-catenin and syndecan-1 were evaluated by digital morphometry and K-RAS, EGFR mutations in FLC cases using paraffin-embedded samples. All FLCs were positive for HepPar1 (HSA) and cytokeratins 7, 8, 18, but negative for cytokeratin 19 by immunohistochemistry. EGFR was significantly overexpressed in all three tumor types, being highest in FLCs (p = 0,0001). EGFR, K-RAS mutation analyses revealed no mutations in exons studied in FLCs. Our findings proved that expression of EGFR is higher in FLC than in other types of primary malignant hepatic tumors and no K-RAS mutation can be detected, so FLC is a good candidate for anti-EGFR treatment.

Increased Expression of Claudin-1 and Claudin-7 in Liver Cirrhosis and Hepatocellular Carcinoma

Claudins have been reported to be differentially regulated in malignancies and implicated in the process of carcinogenesis and tumor progression. Claudin-1 has been described as key factor in the entry of hepatitis C virus (HCV) into hepatocytes and as promoter of epithelial-mesenchymal transition in liver cells. The objective of the current study was to characterize claudin expression in hepatocellular carcinoma (HCC) as well as HCC-surrounding and normal liver samples with respect to cirrhosis and HCV infection. Expression of claudin-1, -2, -3, -4, and −7 was measured by morphometric analysis of immunohistochemistry, and Western blotting in 30 HCCs with 30 corresponding non-tumorous tissues and 6 normal livers. Claudin-1 and −7 protein expression was found significantly elevated in cirrhosis when compared with non-cirrhotic liver. HCCs developed in cirrhotic livers showed even higher expression of claudin-1 contrary to decreased claudin-7 expression when compared with cirrhosis. With reference to HCV status, HCCs or surrounding livers of HCV-infected samples did not show significant alterations in claudin expression when compared with HCV-negative specimens. Cirrhotic transformation associates with elevated claudin-1 and -7 expressions in both non-tumorous liver and HCC. The fact that no significant differences in claudin expression were found regarding HCV-positivity in our sample set suggests that HCV infection alone does not induce a major increase in the total amount of its entry co-factor claudin-1. Increased expression of claudin-1 seems to be a consequence of cirrhotic transformation and might contribute to a more effective HCV entry and malignant transformation.

Claudins and Ki-67: Potential Markers to Differentiate Low- and High-Grade Transitional Cell Carcinomas of the Urinary Bladder

Updated classification of urothelial cell cancer differentiates low-grade and high-grade cancers, which determines potential clinical outcome. Substantial interobserver variability necessitates new biomarkers to ensure classification. Claudins’ specific expression pattern characterizes normal tissues, different tumor types, and defined grades of tumor differentiation. The aim of this study was to examine the expression pattern of claudins and proliferation marker Ki-67 in low-grade and high-grade urothelial cell cancers compared with independent control samples of non-tumorous urothelium, as well as to reveal the predictive usefulness of claudins. The expression of claudins-1, -2, -3, -4, -5, -7, and -10 and Ki-67 was studied with quantitative immunohistochemistry and real-time RT-PCR with relative quantification in 103 samples: 86 urothelial cell cancers (27 low grade, 59 high grade) and 17 non-tumorous urothelia. Results were analyzed regarding overall survival and recurrence-free period as well. High-grade tumors overall showed significantly higher claudin-4 and Ki-67 and significantly lower claudin-7 expression when compared with low-grade ones. High-grade tumors revealed significantly shorter overall survival in Kaplan-Meier analysis. Claudin-4, claudin-7, and Ki-67 might be used as potential markers to differentiate low-grade and high-grade urothelial cell cancers, thereby possibly enhancing accuracy of pathological diagnosis and adding further information to clinical outcome.

Experiences in treatment and follow up of 50 patients with penile cancer

INTRODUCTION Malignant tumour of the penis is a rare disease. Although most of the cases are squamous cell carcinoma histologically, operation is managed by the urologist because of its location. AIM AND METHOD Experience with the treatment and attendance of penile cancer is presented by the author. Results were both retrospectively and prospectively worked up. RESULTS Between June 1996 and June 2006 there was operation performed in 50 patients. Mean age of men was 63.1 (31-83) years. Ninety-four percent of tumours were squamous cell carcinoma, 2 (4%) verrucosus carcinoma, in one case malignant melanoma. Pathological T stadium was T1 in 23 cases (46%), T2 in 19 (38%) patients, in 6 (12%) cases T3 and in 1 (2%) T4. Differentiation was grade 1 in 12 (24%), grade 2 in 27 (54%) and grade 3 in 10 (20%) cases. One side inguinal lymph node metastases were found in 11 (22%) and both side in 8 (16%) patients. In anamnesis 4 (8%) patients underwent circumcision because of phimosis, and 25 (50%) patients had had phimosis by identification of cancer. Seventeen patients (34%) were given chemotherapy after surgical treatment. Mean survival time of all patients was 31,4 (2-114) months. CONCLUSION Phimosis plays an important role in development of penile cancer, thats surgical treatment does not prevent the higher chance of incidence rate. The disease behaves aggressively, spreading through lymphatic vessels, where in advanced stadium, or in low differentiation cases it is already demonstrable by diagnosis. In the choice of therapy, stadium-oriented principle should be predominant. With early operation, long-term survival can be achieved.

Hímvessző-daganatos betegek kezelésével szerzett tapasztalataink@@@Experiences in treatment and follow up of 50 patients with penile cancer

INTRODUCTION Malignant tumour of the penis is a rare disease. Although most of the cases are squamous cell carcinoma histologically, operation is managed by the urologist because of its location. AIM AND METHOD Experience with the treatment and attendance of penile cancer is presented by the author. Results were both retrospectively and prospectively worked up. RESULTS Between June 1996 and June 2006 there was operation performed in 50 patients. Mean age of men was 63.1 (31-83) years. Ninety-four percent of tumours were squamous cell carcinoma, 2 (4%) verrucosus carcinoma, in one case malignant melanoma. Pathological T stadium was T1 in 23 cases (46%), T2 in 19 (38%) patients, in 6 (12%) cases T3 and in 1 (2%) T4. Differentiation was grade 1 in 12 (24%), grade 2 in 27 (54%) and grade 3 in 10 (20%) cases. One side inguinal lymph node metastases were found in 11 (22%) and both side in 8 (16%) patients. In anamnesis 4 (8%) patients underwent circumcision because of phimosis, and 25 (50%) patients had had phimosis by identification of cancer. Seventeen patients (34%) were given chemotherapy after surgical treatment. Mean survival time of all patients was 31,4 (2-114) months. CONCLUSION Phimosis plays an important role in development of penile cancer, thats surgical treatment does not prevent the higher chance of incidence rate. The disease behaves aggressively, spreading through lymphatic vessels, where in advanced stadium, or in low differentiation cases it is already demonstrable by diagnosis. In the choice of therapy, stadium-oriented principle should be predominant. With early operation, long-term survival can be achieved.

Hímvesszo-daganatos betegek kezelésével szerzett tapasztalataink

INTRODUCTION Malignant tumour of the penis is a rare disease. Although most of the cases are squamous cell carcinoma histologically, operation is managed by the urologist because of its location. AIM AND METHOD Experience with the treatment and attendance of penile cancer is presented by the author. Results were both retrospectively and prospectively worked up. RESULTS Between June 1996 and June 2006 there was operation performed in 50 patients. Mean age of men was 63.1 (31-83) years. Ninety-four percent of tumours were squamous cell carcinoma, 2 (4%) verrucosus carcinoma, in one case malignant melanoma. Pathological T stadium was T1 in 23 cases (46%), T2 in 19 (38%) patients, in 6 (12%) cases T3 and in 1 (2%) T4. Differentiation was grade 1 in 12 (24%), grade 2 in 27 (54%) and grade 3 in 10 (20%) cases. One side inguinal lymph node metastases were found in 11 (22%) and both side in 8 (16%) patients. In anamnesis 4 (8%) patients underwent circumcision because of phimosis, and 25 (50%) patients had had phimosis by identification of cancer. Seventeen patients (34%) were given chemotherapy after surgical treatment. Mean survival time of all patients was 31,4 (2-114) months. CONCLUSION Phimosis plays an important role in development of penile cancer, thats surgical treatment does not prevent the higher chance of incidence rate. The disease behaves aggressively, spreading through lymphatic vessels, where in advanced stadium, or in low differentiation cases it is already demonstrable by diagnosis. In the choice of therapy, stadium-oriented principle should be predominant. With early operation, long-term survival can be achieved.