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Clinical Study

Expression of Dystroglycan Correlates with Tumor Grade and Predicts Survival in Renal Cell Carcinoma

A. Sgambato, A. Camerini, D. Amoroso, G. Genovese, F. De Luca, M. Cecchi, M. Migaldi, A. Rettino, C. Valsuani, G. Tartarelli, S. Donati, O. Siclari, G. Rossi and A. Cittadini

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The dystroglycan (DG) complex is a transmembrane glycoprotein that forms a continuous link from the extracellular matrix to the actin cytoskeleton. Deregulated expression of DG has been reported in a variety of human malignancies and related to tumor aggressiveness. In this study expression of the α-DG subunit was evaluated by immunostaining in a series of renal epithelial cancers and its relation with traditional prognostic indicators and with the clinical outcome of the patients was evaluated. α-DG expression was undetectable in a significant fraction of tumors (54%). In renal cell carcinomas (RCC) loss of DG staining correlated with higher tumor grade (p = 0.02) but not with tumor stage nor tumor size. In clear cell RCC patients loss of α-DG staining correlated with an increased risk of recurrence (p = 0.002 by log-rank test) and death (p = 0.004) also when patients with lower grade or stage tumors were analyzed separately. In a multivariate analysis loss of DG staining confirmed to be and independent predictor of shorter disease-free (p = 0.001; RR = 4.9) and overall (p = 0.009; RR = 4.9) survival stronger than tumor grade and size. These findings demonstrate that loss of α-DG expression, which correspond to loss of a functional DG complex, is a frequent event in human renal tumorigenesis and is an independent predictor of early recurrence and death for patients with clear cell RCC.

Authors

A. Sgambato

Centro di Ricerche Oncologiche %u201CGiovanni XXIII%u201D-Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, Rome, Italy

A. Camerini

Centro di Ricerche Oncologiche %u201CGiovanni XXIII%u201D-Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, Rome, Italy

D. Amoroso

Centro di Ricerche Oncologiche %u201CGiovanni XXIII%u201D-Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, Rome, Italy

G. Genovese

Centro di Ricerche Oncologiche %u201CGiovanni XXIII%u201D-Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, Rome, Italy

F. De Luca

U.O.C. di Urologia, Ospedale Unico %u201CVersilia%u201D, Viareggio, Italy.

M. Cecchi

U.O.C. di Urologia, Ospedale Unico %u201CVersilia%u201D, Viareggio, Italy.

M. Migaldi

Dipartimento Misto di Anatomia Patologica e di Medicina Legale, Sezione di Anatomia Patologica, University of Modena and Reggio Emilia, Modena, Italy

A. Rettino

Centro di Ricerche Oncologiche %u201CGiovanni XXIII%u201D-Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, Rome, Italy

C. Valsuani

Istituto Toscano Tumori, U.O.C. Oncologia Medica, Ospedale Unico %u201CVersilia%u201D, Viareggio, Italy.

G. Tartarelli

Istituto Toscano Tumori, U.O.C. Oncologia Medica, Ospedale Unico %u201CVersilia%u201D, Viareggio, Italy.

S. Donati

Istituto Toscano Tumori, U.O.C. Oncologia Medica, Ospedale Unico %u201CVersilia%u201D, Viareggio, Italy.

O. Siclari

Istituto Toscano Tumori, U.O.C. Oncologia Medica, Ospedale Unico %u201CVersilia%u201D, Viareggio, Italy.

G. Rossi

Dipartimento Misto di Anatomia Patologica e di Medicina Legale, Sezione di Anatomia Patologica, University of Modena and Reggio Emilia, Modena, Italy

A. Cittadini

Centro di Ricerche Oncologiche %u201CGiovanni XXIII%u201D-Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, Rome, Italy

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