Clinical Importance of Focal Adhesion Kinase (FAK)-Src and Paxillin Expression in Renal Cell Carcinoma.

BACKGROUND AND OBJECTIVE: The complex focal adhesion kinase (FAK)/Src and paxillin seem to play a key role in the pathogenesis and progression of cancer. The aim of this study is to evaluate the expression of these proteins in renal cell carcinomas (RCCs), considering the immunoreactive score (IRS), the positivity and the intensity, and to find any association with patients' clinical characteristics, histologic type and other pathological features that imply a possible pathophysiological or prognostic role of FAK/Src and paxillin in RCC. METHODS: Patients with RCC who had undergone partial or radical nephrectomy from January 2009 to September 2010 were eligible for this retrospective cross-sectional study. The immunohistochemical expression of FAK, Src and paxillin proteins in formalin-fixed paraffin-embedded tumour tissue was analysed in association with various clinicopathological features. RESULTS: Out of ninety patients, 58 had clear cell renal carcinoma, 15 had papillary, 11 had chromophobe and six had unclassified RCC. FAK, Src and paxillin were expressed in 55.6%, 32.2% and 18.9% of all cases, respectively. In univariate analysis, FAK positivity and IRS were more likely in patients with papillary and chromophobe histologic type versus clear cell RCC (p<0.005), Src positivity and IRS presented more frequently in stage T3 versus T1 (p<0.005) and paxillin positivity was more likely in patients with stage T3 versus T2 (p=0.021) and grades 3-4 versus grade 2 (p=0.013). Paxillin-IRS was not associated with any clinicopathological features. The same associations were also reproduced in the multifactorial analysis for the FAK and Src positivity and IRS, while it was found that paxillin positivity and IRS were associated with the female gender (p=0.052, p=0.024), and were higher in grades 3-4 versus grade 2 (p=0.022, p=0.020). CONCLUSIONS: Our study suggests that RCC shows immunohistochemical expression of FAK, Src and paxillin proteins, and this expression varies in relation to the histologic type, the stage and the stage/grade/gender, respectively. These findings imply a possible involvement of the FAK/Src signalling pathway in the pathogenesis and progression of cancer in RCC, providing future perspectives for targeted therapies with inhibitors.

Clinical Importance of Cannabinoid Type 1 Receptor (CB1R) and Cannabinoid Type 2 Receptor (CB2R) Expression in Renal Cell Carcinoma.

Background and objective The purpose of our study was to assess the expression of cannabinoid type 1 receptor (CB1R) and cannabinoid type 2 receptor (CB2R), including positivity, intensity, percentage, site of distribution, and immunohistochemical score, in renal cell carcinomas (RCCs) and explore their correlation with various clinicopathological aspects. Methodology We retrospectively obtained data and specimens from 87 patients diagnosed with RCC after partial or radical nephrectomy, and the CB1R and CB2R expression was assessed immunohistochemically on paraffin-embedded tissues. The results were statistically analyzed uni- and multi-factorial along with clinicopathological parameters. Results CB1R was not expressed at all, and CB2R was highly expressed in 78 (89.7%) patients with RCC. In unifactorial analysis, no statistical significance was found in any of the analyzed parameters. However, in the multifactorial analysis, we found that patients with a papillary histologic type (P < 0.0005) were associated with a lower likelihood of expression of the CB2R in the membranous compared with those with clear-cell and were also associated with a higher likelihood of moderate or strong expression of CB2R immunohistochemical score compared with those with clear-cell (P = 0.03). Patients with stage T2 (P = 0.010) had more enhanced expression (grade 3 CB2R intensity) compared with those with stage T1. Males (beta coefficient ± standard error [SE] 13.70 ± 7.04; P = 0.056) and patients with chromophobe histologic type (beta coefficient ± SE 23.45 ± 9.86; P = 0.020) were associated with a higher percentage of CB2R expression. Conclusions Our data suggest that although the CB1R was not expressed in RCCs, CB2R was expressed in almost every patient and enhanced expression was noted in correlation with specific clinicopathological aspects of the patients. Thus, following well-designed studies, especially CB2R could be used as a prognostic marker or even as a potential therapeutic target in RCC.

Flow resistive forces index (QRF): Development and clinical applicability assessment of a novel measure of bladder outlet resistance, aiming to enhance the diagnostic performance of uroflowmetry.

BACKGROUND: Currently, the diagnostic ability of uroflowmetry, the most widely used urodynamic test available for initial assessment of patients with lower urinary tract symptoms (LUTS), is considered limited by its inability to accurately discriminate between the underlying mechanisms of this condition. To improve the diagnostic accuracy of uroflow, we developed a mathematical formula that calculates the flow resistive forces index (QRF), a novel measure of bladder outflow/urethral resistance, and assessed its clinical applicability compared to the maximum flow rate (Qmax ). MATERIALS AND METHODS: A cross-sectional observational study was conducted in a cohort of 61 adult men presenting with voiding dysfunction symptoms, who all underwent free uroflowmetry followed by pressure flow study. The development of the mathematical formula which contains five key uroflowmetry variables (voided volume, flow time, Qmax , average flow rate, and peak flow time) was based on the assumption that urine volume momentum changes during voiding, the concept of diphasic uroflow pattern (acceleration/deceleration), and the urethral resistance factor (URA) equation. Study subjects were classified either as obstructed or nonobstructed according to established urodynamic criteria (linearized passive urethral resistance relation, LinPURR; Abrams-Griffiths number, AGN [also called bladder outlet obstruction index, BOOI]; and URA). Univariate linear correlations, binary logistic regression model, and receiver operating characteristic (ROC) curve statistical analysis were employed (SPSS-22, MedCalc, GraphPad [P < .05]). RESULTS: Outflow obstruction was diagnosed in 50.8% (1 in 2) patients. Univariate analysis, and bivariate linear correlation, binary logistic regression, and ROC curve analyses showed that the QRF was a strong independent predictor of bladder outlet/outflow obstruction (BOO), significantly outperforming Qmax . CONCLUSIONS: QRF index accurately predicts BOO, significantly outperforming the currently widely used bladder outlet obstruction estimator Qmax . Despite potential study limitations (mainly small cohort size and lack of control group), we anticipate that with further study and proper clinical validation, QRF could become a valuable complement to uroflowmetry.

Synchronous Bilateral Testicular Tumors with Different Histopathology.

A 40-year-old male presented to our outpatient department with the chief complaint of a painless mass on his right testis with gradual size increase over the past two months. Physical examination and ultrasound revealed a firm and nontender mass both on the right and on the left testis. The only elevated biomarker was b-hcG (24,7 mIU/mL) and computer tomography (CT) did not reveal any pathology. Bilateral high orchiectomies were performed, without previous frozen storage of the sperm. Histology proved typical seminoma of the left testis and embryonal carcinoma of the right testis. He received two cycles of adjuvant combination chemotherapy with bleomycin, etoposide, and cisplatin. Six months after the operation no residual tumor or recurrence was observed.