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Claudin-1 Protein Expression is a Prognostic Marker of Patient Survival in Renal Cell Carcinomas

Authors' Affiliations: ¹ Institute of Pathology and ² Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany; and ³ Institute of Surgical Pathology, UniversitätsSpital Zürich, Zurich, Switzerland

Requests for reprints: Glen Kristiansen, Institute of Surgical Pathology UniversitätsSpital Zürich, 8091 Zurich, Switzerland. Phone: 41-44-255-3457; Fax: 41-44-255-4416; E-mail: glen.kristiansen{at}usz.ch.

Purpose: Claudin-1 is a tight junction protein described in normal tissues as well as in malignancies. We aimed to assess the diagnostic or prognostic significance of claudin-1 expression in renal cell carcinoma and to correlate the expression of claudin-1 with clinical, histopathologic, and prognostic parameters in renal cell carcinoma.

Experimental Design: A tissue microarray was constructed using formalin-fixed, paraffin-embedded tissue from renal cell carcinomas and corresponding normal renal tissue from 318 patients. The protein expression of claudin-1 was assessed and correlated to clinicopathologic tumor parameters including patient survival. A separate cohort of 44 papillary renal cell carcinoma was used for validation of results.

Results: Claudin-1 was expressed in 29.9% of renal cell cancer cases. Whereas the vast majority of clear cell carcinomas were negative for claudin-1, most papillary tumors (76-86%) were positive. Claudin-1 expression was associated with markers of unfavorable tumor biology in clear cell renal cell carcinoma, whereas the opposite was valid for papillary renal cell carcinoma. In clear cell renal cell carcinoma claudin-1 positivity was a prognosticator of shortened disease-specific patient survival in univariate analysis (P = 0.008), which also remained significant in multivariate analyses in the clinically important subgroups of nonmetastasized or asymptomatic patients.

Conclusions: Claudin-1 is expressed in the majority of papillary renal cell carcinomas, suggesting a diagnostic value of this marker. Its expression is an independent prognosticator of shortened disease-specific patient survival in clinically relevant subgroups of clear cell renal cell carcinoma. Further functional studies are needed to clarify the different biological roles of claudin-1 expression in these histologic subtypes of renal cell carcinoma.