BackgroundFibronectin 1 (FN1) is a glycoprotein involved in cellular adhesion and migration processes. The aim of this study was to elucidate the role of FN1 in development of renal cell cancer (RCC) and to determine a prognostic relevance for optimal clinical management.Methods212 renal tissue samples (109 RCC, 86 corresponding tissues from adjacent normal renal tissue and 17 oncocytomas) were collected from patients undergoing surgery for renal tumors and subjected to total RNA extraction. Detection of FN1 mRNA expression was performed using quantitative real time PCR, three endogenous controls, renal proximal tubular epithelial cells (RPTEC) as biological control and the ΔΔCt method for calculation of relative quantities.ResultsMean tissue specific FN1 mRNA expression was found to be increased approximately seven fold comparing RCC and corresponding kidney control tissues (p < 0.001; ANOVA). Furthermore, tissue specific mean FN1 expression was increased approx. 11 fold in clear cell compared to papillary RCC (p = 9×10-5; Wilcoxon rank sum test). Patients with advanced disease had higher FN1 expression when compared to organ-confined disease (p < 0.001; Wilcoxon rank sum test). Applying subgroup analysis we found a significantly higher FN1 mRNA expression between organ-confined and advanced disease in the papillary and not in the clear cell RCC group (p = 0.02 vs. p = 0.2; Wilcoxon rank sum test). There was an increased expression in RCC compared to oncocytoma (p = 0.016; ANOVA).ConclusionsTo our knowledge, this is the first study to show that FN1 mRNA expression is higher in RCC compared to normal renal tissue. FN1 mRNA expression might serve as a marker for RCC aggressiveness, indicating early systemic progression particularly for patients with papillary RCC.

BackgroundCaveolae play a significant role in disease phenotypes such as cancer, diabetes, bladder dysfunction, and muscular dystrophy. The aim of this study was to elucidate the caveolin-1 (CAV1) protein expression in renal cell cancer (RCC) and to determine its potential prognostic relevance.Methods289 clear cell RCC tissue specimens were collected from patients undergoing surgery for renal tumors. Both cytoplasmic and membranous CAV1 expression were determined by immunohistochemistry and correlated with clinical variables. Survival analysis was carried out for 169 evaluable patients with a median follow up of 80.5 months (interquartile range (IQR), 24.5 - 131.7 months).ResultsA high CAV1 expression in the tumor cell cytoplasm was significantly associated with male sex (p = 0.04), a positive nodal status (p = 0.04), and poor tumor differentiation (p = 0.04). In contrast, a higher than average (i.e. > median) CAV1 expression in tumor cell membranes was only linked to male sex (p = 0.03). Kaplan-Meier analysis disclosed significant differences in 5-year overall (51.4 vs. 75.2%, p = 0.001) and tumor specific survival (55.3 vs. 80.1%, p = 0.001) for patients with higher and lower than average cytoplasmic CAV1 expression levels, respectively. Applying multivariable Cox regression analysis a high CAV1 protein expression level in the tumor cell cytoplasm could be identified as an independent poor prognostic marker of both overall (p = 0.02) and tumor specific survival (p = 0.03) in clear cell RCC patients.ConclusionOver expression of caveolin-1 in the tumour cell cytoplasm predicts a poor prognosis of patients with clear cell RCC. CAV1 is likely to be a useful prognostic marker and may play an important role in tumour progression. Therefore, our data encourage further investigations to enlighten the role of CAV1 and its function as diagnostic and prognostic marker in serum and/or urine of RCC patients.

Abstract. Fibronectin 1 (FN1) is a glycoprotein that is involved in cell adhesion and migration processes including embryogenesis, wound healing, blood coagulation, host defenses and metastasis. The aim of this study was to elucidate the FN1 protein expression in renal cell carcinoma (RCC) and to determine its potential prognostic relevance. A total of 270 clear cell RCC tissue specimens were collected from patients undergoing surgery for renal tumors. Biomarker expression was determined by immunohistochemistry and correlated with clinical variables. Survival analysis was carried out for 153 patients with complete follow-up data and pathologically proven clear cell carcinoma of the kidney. The follow-up group had a mean follow-up period of 83.8 months (IQR 26.2-136.2 months). The calculated median 5-year overall and tumor-specific survival rate of all 153 evaluable patients was 66.6 and 71.0%, respectively. A higher diseaserelated mortality rate was observed among patients with cytoplasmic FN1 expression (41.3 vs. 24.7%, p=0.039, Fisher's exact test). No significant correlation was found between FN1 staining and patient characteristics such as age, gender, tumor differentiation and visceral metastasis. However, there was a trend for FN1 expression and correlation with tumor stage and lymph node metastasis (p=0.085 and p=0.203; respectively). The Kaplan-Meier analysis revealed significant differences in the 5-year tumor-specific survival for patients with and without cytoplasmic FN1 expression (64.8 vs. 77.7%; p=0.035, log-rank test). However, results of the multivariate Cox regression analysis showed that FN1 expression was not an independent marker of either overall or tumor-specific survival. In conclusion, FN1 protein expression in RCC is associated with a higher disease-related mortality rate, indicating a possible role in RCC progression. Therefore, our data on FN1 encourage further investigations to determine the role of FN1 in RCC.