Galectin-1 and Galectin-3 mRNA expression in renal cell carcinoma.

BACKGROUND: Galectins are known to regulate cell differentiation and growth as well as cell adhesion and apoptosis. Galectins have been discussed as possible prognosticators for survival in renal cell cancer (RCC) and other urological tumors. They might also play an emerging role as possible new marker-proteins for RCC. In this study, we analyzed the expression of galectin-1 and galectin-3 mRNA in order to further investigate their clinical significance in RCC. METHODS: Tissue samples were obtained from 106 patients undergoing surgery for RCC. The expression of galectin-1 and galectin-3 mRNA in normal kidney and corresponding cancer tissue was analyzed using quantitative real time PCR. Differences in expression levels of paired tissue samples were assessed using paired two-sample tests. Associations of relative mRNA expression levels in tumor tissues with clinical findings were analyzed using univariate logistic regression. RESULTS: The expression of galectin-1 (p < 0.001) and -3 (p < 0.001) mRNA were significantly higher in RCC when compared to the adjacent normal kidney tissue. For clear cell RCC, an association of male gender with higher galectin-1 and galectin-3 mRNA expression (p = 0.054, p = 0.034) was detected. For all RCCs, galectin-1 mRNA expression failed to show a significant association with advanced disease as well as a higher rate of lymph node metastases (p = 0.058, p = 0.059). CONCLUSION: The mRNA expression of galectin-1 and galectin-3 is significantly increased in RCC cancer tissue. The higher mRNA expression in tumor tissue of male patients raises the question of a functional connection between galectins and the higher prevalence of RCC in men. Associations with advanced disease might lead to new ways of identifying patients at higher risk of recurrent disease and might even facilitate early metastasectomy with curative intent.

GATA5 CpG island hypermethylation is an independent predictor for poor clinical outcome in renal cell carcinoma.

Transcriptional inactivation and CpG island (CGI) methylation of GATA transcription factor family members GATA3 and GATA5 have been reported for a few types of human cancer. Whether high-density CGI methylation of GATA3 or GATA5 is associated with the clinical course of patients with renal cell cancer (RCC) has not been clarified. Quantitative methylation-specific PCR assays were carried out to analyze 25 tumor cell lines including 6 RCC lines and 119 RCC and 87 adjacent normal tissues for the presence of densely methylated sequences. Methylation values were statistically compared with clinicopathological and recurrence-free survival (RFS) data for patients. Comparison of GATA3 and GATA5 methylation in different tumor cell lines revealed a marker-specific methylation characteristic with high and frequent signals for both methylation marks in RCC lines. GATA3 and GATA5 CGI relative methylation levels were found to be strongly associated with the state of metastasis (P=0.003 and P<0.001, respectively) and advanced disease (P=0.024 and P<0.001, respectively). Moreover, an independent decrease in RFS in Cox proportional hazard analysis was found for tumors exhibiting high GATA5 methylation (P<0.001, hazard ratio, 19.3; 95% confidence interval, 4.58-81.6). Epigenetic alterations in GATA family members may be associated with aggressive tumor phenotypes in RCC, and in the case of GATA5, may serve as a new independent molecular marker for aggressiveness and disease progression.

PTEN and p27Kip1 are not downregulated in the majority of renal cell carcinomas--implications for Akt activation.

Activation of the PKB/Akt pathway is supposed to substantially contribute to the pathogenesis and progression of malignant disease. The present study aimed at determining the occurrence of an impaired PTEN and p27Kip1 expression alone or in combination in a renal cell carcinoma to further clarify the role of Akt-pathway-associated proteins for the development and/or progression of this malignant disease. By using tissue microarray analysis, tissue samples from renal cell cancers and the corresponding benign tissue samples were investigated for expression of the PTEN, pAkt and p27Kip1 protein by immunohistochemistry. Additionally, a Western blot and RT-PCR analysis was performed to verify the results obtained from the immunohistochemical approach and to further clarify the mechanisms underlying the regulation of both proteins in renal cell cancer. Western blot analysis revealed an overexpression of PTEN and p27Kip1 in renal cell cancer samples and a significantly elevated expression of both proteins when compared with the corresponding benign tissue (p<0.0001 and p<0.0005). The latter finding was confirmed by real-time RT-PCR (p<0.05 and p<0.01) and immunohistochemistry (p<0.001 and p<0.0001). PTEN and p27Kip1 expression were positively correlated with each other both in the tumour and benign tissue (p<0.001 and p<0.0001). We concluded that a strong expression of PTEN in renal cell cancer did not block the PI3K-mediated phosphorylation of Akt in the tumour specimens analysed. Furthermore, Akt activation may not result in a decreased p27Kip1, the latter being retained and overexpressed in the majority of renal cell cancers when compared with the corresponding benign renal parenchyma.