Attila Szendroi

Gene network and canonical pathway analysis in prostate cancer: a microarray study

The molecular mechanism playing a role in the development of prostate cancer (PCA) is not well defined. We decided to determine the changes in gene expression in PCA tissues and to compare them to those in noncancerous samples. Prostate tissue samples were collected by needle biopsy from 21 PCA and 10 benign prostate hyperplasic (BPH) patients. Total RNA was isolated, cDNA was synthesized, and gene expression levels were determined by microarray method. In the progression to PCA, 738 up-regulated and 515 downregulated genes were detected in samples. Analysis using Ingenuity Pathway Analysis (IPA) software revealed that 466 network and 423 functions-pathways eligible genes were up-regulated, and 363 network and 342 functions-pathways eligible genes were down-regulated. Up-regulated networks were identified around IL-1β and insulin-like growth factor-1 (IGF-1) genes. The NFKB gene was centered around two upand down-regulated networks. Up-regulated canonical pathways were assigned and four of them were evaluated in detail: acute phase response, hepatic fibrosis, actin cytoskeleton, and coagulation pathways. Axonal guidance signaling was the most significant down-regulated canonical pathway. Our data provide not only networks between the genes for understanding the biologic properties of PCA but also useful pathway maps for future understanding of disease and the construction of new therapeutic targets.

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.

MicroRNAs with Prognostic Potential for Metastasis in Clear Cell Renal Cell Carcinoma: A Comparison of Primary Tumors and Distant Metastases

AbstractBackground MicroRNAs (miRNAs) are regulators of gene expression in tumor development and progression. However, their influence on metastasis of clear cell renal cell carcinoma (ccRCC) is less understood. To determine the role of miRNAs in metastatic progression, miRNA expression in primary ccRCC was compared to distant metastases. MethodsTotal RNA of 53 primary ccRCCs, 35 distant metastases from lung, bone, brain, and abdomen, as well as 17 normal kidney tissues was isolated from fresh frozen tissue and formalin-fixed paraffin-embedded (FFPE) samples. The miRNA microarrays were performed based on fresh frozen tissue. Results were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on fresh frozen tissue and FFPE samples. Real-time cell analyses and transwell invasion assays were carried out after transient transfection of microRNA-30c (miR-30c) in cell line 786-O.ResultsThere were 14 miRNAs differently expressed in metastatic primary ccRCC and distant metastases compared to non-metastatic primary tumors. A strong correlation of miRNAs to progression-free- and cancer-specific 5-year-survival was determined. Specific miRNAs were differently expressed in distant metastases compared to primary ccRCC. A miRNA signature distinguished lung metastases from other metastatic sites. Overexpression of miR-30c increased adherence and decreased migration and invasion in the ccRCC cell line.ConclusionsMiRNAs are deregulated in metastatic primary ccRCC and could be promising prognostic markers for an early prediction of metastasis. Alterations in miRNA expression characterize distant metastases of different metastatic sites. Furthermore, our study suggests a functional role of miR-30c in metastasis. The miRNAs could be a helpful tool for individual follow-up prediction and personalized therapy selection.

Clear cell renal cell carcinoma and papillary renal cell carcinoma: differentiation of distinct histological types with multiphase CT.

PURPOSE Conventional clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) have different behavioral characteristics and clinical management strategies (nephrectomy vs. nephron-sparing surgery). Our aim was to retrospectively evaluate the contrast enhancement pattern of ccRCC and pRCC and evaluate its possible diagnostic role for preoperative differentiation using a standardized protocol. MATERIALS AND METHODS Quadriphasic multidetector computed tomography (CT) images (unenhanced, corticomedullary, nephrographic, and excretory phases) of 19 patients with 20 ccRCC and 14 patients with 15 pRCC lesions (mean ages, 62.3±14.1 and 61.4±13.7 years, respectively) were reviewed retrospectively. The attenuation characteristics were compared with the attenuation of the normal renal cortex using either multiple 10 mm2 regions of interest or whole tumor attenuation measurements. The degree of contrast enhancement was also compared. RESULTS Univariate analysis revealed that ccRCC lesions showed higher mean attenuation values on the corticomedullary and nephrographic phases compared with pRCC masses (P < 0.05) using both measurement techniques. CONCLUSION The findings underscore the importance of multiphase CT in the differentiation of these two subtypes of RCC using standard assessment techniques. The measurement of the degree of enhancement on contrast-enhanced multidetector CT may be a simple and useful method to radiologically differentiate between the two histological types of RCC.

β-catenin expression and claudin expression pattern as prognostic factors of prostatic cancer progression

To investigate the patterns of expression of the junctional proteins β‐catenin and claudins in different prognostic groups of patients with prostatic cancer, to determine their value as prognostic markers.

Mutations of KRAS, NRAS, BRAF, EGFR, and PIK3CA genes in urachal carcinoma: Occurence and prognostic significance

Purpose Targeted therapy represents an attractive alternative for rare tumors such as urachal carcinoma (UrC). The aim of this study was to assess the mutations of the most commonly affected 5 genes in the targetable EGFR-pathway in UrC and comapre their frequencies to those of found in urothelial and colorectal cancer. Materials and Methods Mutational hot-spots of selected genes were tested in 22 UrC samples by pyrosequencing. Mutational patterns were compared to those published for colorectal and urothelial cancers. Furthermore, we sought correlations between mutations and clinicopathological and follow-up data. Results We found 11 mutations in 10 of 22 (45%) patients. The most frequently mutated gene was KRAS (27%) followed by BRAF (18%) and NRAS (5%), while no mutations were detected in the EGFR and PIK3CA genes. No correlation was found between the mutation status and clinicopathological parameters (Sheldon/Mayo stage, tumor grade, metastases). Furthermore, none of the mutations correlated with progression-free or overall survival. Conclusions The mutation pattern of UrC is more similar to colorectal than to urothelial cancer. However, the mutation characteristics of UrC seems to be unique suggesting that clinical decision-making for UrC cannot be simply adopted from urothelial or colorectal carcinoma. The high occurence of EGFR-pathway mutations warrants the testing for KRAS and BRAF mutations when considering anti-EGFR therapy in UrC.

Transitional cell and clear cell renal carcinoma: Differentiation of distinct histological types with multiphase CT

Background Transitional cell carcinoma (TCC) may mimic renal cell carcinoma (RCC) when it develops in a similar location, therefore, differentiation with imaging techniques might be challenging. Preoperative differentiation may have a significant role indicating the type of surgical treatment (nephrectomy vs. ureteronephrectomy). Purpose To retrospectively analyze the differences in the contrast enhancement of TCC and RCC. Material and Methods Images of 20 RCC and 12 TCC (mean ages, 62.3 ± 14.1 and 67.4 ± 12.0 years, respectively) were analyzed from patients who underwent multiphase computed tomography (CT) examinations following 1.5 mL/kg non-ionic contrast agent administration. Unenhanced corticomedullary (30–45 s), nephrographic (70–90 s), and excretory (300–480 s) phases were imaged. The attenuation characteristics of RCC and TCC were compared to the attenuation of the normal renal cortex. Results Significant differences were found in the attenuation ratios between RCC or TCC in the corticomedullary (P = 0.040) and nephrographic (P = 0.004) phases using three regions of interest (ROIs) of 10 mm2 size. If measuring ROIs comprising the complete tumor lesion instead of three small ROIs, no significant difference was observed in the attenuation ratios between RCC in TCC in any phases. Conclusion Our study reports significant attenuation differences between RCC and TCC in the corticomedullary and nephrographic phases by multiphase CT. The findings underscore the importance of multiphase CT in the differentiation of these two different entities. Using multiple small (three) ROIs is more accurate than measuring the whole tumor attenuation.

Renal tumor causing haematuria and sepsis

A 28 year old female patient developed hematuria in the 32th week of her pregnancy. She was given antibiotic treatment, since a urinary tract infection was suspected. After delivery symptoms of acute pyelonephritis, then sepsis developed, and conservative therapy had no effect. Ultrasound examination showed unusual renal destruction, so nephrectomy was performed. Surgical intervention revealed the presence of an advanced tumor of the kidney, while histological examination confirmed a Bellini duct carcinoma of the kidney.

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.