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The L1 Cell Adhesion Molecule Is Induced in Renal Cancer Cells and Correlates with Metastasis in Clear Cell Carcinomas

¹ Institut National de la Santé et de la Recherche Médicale U489 and ² Department of Pathology, Tenon Hospital (Assistance Publique-Hôpitaux de Paris) and Paris 6 University, Paris, France and ³ Department of Cell Biology Institute of Anatomy, University of Aarhus, Denmark

Requests for reprints: Hanna Debiec, Institut National de la Sante et de la Recherche Medicale U489, Hôpital Tenon, 4 rue de la Chine, Paris 75020, France. Phone: 33-1-56-01-65-14; Fax: 33-1-56-01-62-17. E-mail: hanna.debiec{at}tnn.ap-hop-paris.fr.

Purpose: The L1 cell adhesion molecule is overexpressed in many human carcinomas. The objectives of the study were to provide a comprehensive description of L1 distribution in human kidney and to establish the prognostic relevance of L1 expression in renal cell carcinomas (RCC).

Experimental Design: Using two antibodies to the extracellular part and the cytoplasmic domain, respectively, we first compared L1 expression in normal kidney and renal tumors of diverse histopathologic origin, then we studied L1 expression together with tumor stage, grade, molecular prognostic biomarkers, and metastatic behavior.

Results: In normal kidney, L1 immunoreactive with both antibodies was expressed in all epithelial cells originating from the ureteric bud except for intercalated cells. In renal tumors, L1 was mainly detected in those originating from cells that do not express L1 in the normal kidney [i.e., 33 of 72 clear cell RCC (ccRCC) and 25 of 88 papillary RCC (papRCC)]. Both in ccRCC and papRCC, L1 reacted only with the antibody to the extracellular domain, suggesting that the protein was truncated. In these carcinomas, L1 expression was strongly correlated with Ki-67 proliferation index (ccRCC, P = 0.0059; papRCC, P = 0.0039), but only in ccRCC, the presence of L1 was associated with the risk of metastasis (P = 0.0121). This risk was higher if cyclin D1 was concurrently absent in tumor cells (P < 0.0001). The L1⁺/cyclin D1^– profile was an independent prognostic factor of metastasis occurrence in multivariate analysis (P = 0.0023).

Conclusion: We have found a combination of markers that can serve to identify a subgroup of high-risk patients with ccRCC that may require more aggressive therapies.

Key Words: prognostic markers • metastasis • tissue microarray • immunohistochemistry

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