Caveolin 1 protein expression in renal cell carcinoma predicts survival

Abstract

Background: Caveolae 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.

Methods: 289 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).

Results: A 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.

Conclusion: Over 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.

Figure 1

Association between cytoplasmic CAV1 expression and clinical outcome in all patients (Kaplan-Meier; n = 169): The overall survival of patients with a higher-than-average CAV1 expression in the tumor cell cytoplasm was significantly shorter compared with that of patients lower CAV1 levels. 5-year survival rates were calculated at 51.4% and 75.2% (p = 0.001, Mantel-Cox).

Figure 2

Association between cytoplasmic CAV1 expression and clinical outcome in all patients (Kaplan-Meier; n = 169): The tumor-specific survival of patients with a higher-than-average CAV1 expression in the tumor cell cytoplasm was significantly shorter compared with that of patients lower CAV1 levels. 5-year survival rates were calculated at 55.3% and 80.1% (p = 0.001, Mantel-Cox).

Figure 3

Association between cell membrane CAV1 expression and clinical outcome in all patients (Kaplan-Meier; n = 169): The overall survival of patients with a higher-than-average CAV1 expression in the tumor cell membrane did not significantly differ from that of patients lower CAV1 levels. 5-year survival rates were calculated at 59.7% and 68.1% (p = 0.41, Mantel-Cox).

Figure 4

Association between cell membrane CAV1 expression and clinical outcome in all patients (Kaplan-Meier; n = 169): The tumor-specific survival of patients with a higher-than-average CAV1 expression in the tumor cell membrane did not significantly differ from that of patients lower CAV1 levels. 5-year survival rates were calculated at 64.4% and 72.5% (p = 0.24, Mantel-Cox).