Expression of dystroglycan correlates with tumor grade and predicts survival in renal cell carcinoma.
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 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. alphaDG expression was undetectable in a significant fraction of tumors (54%). In renal cell carcinomas (RCC) loss of alpha-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 alphaDG 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 alphaDG 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.
Sgambato
Alessandro
A
Centro di Ricerche Oncologiche Giovanni XXIII-Istituto di Patologia General, Università Cattolica del Sacro Cuore, Rome, Italy. asgambato@rm.unicatt.it
Camerini
Andrea
A
Amoroso
Domenico
D
Genovese
Giannicola
G
De Luca
Filomena
F
Cecchi
Massimo
M
Migaldi
Mario
M
Rettino
Alessandro
A
Valsuani
Chiara
C
Tartarelli
Gianna
G
Donati
Sara
S
Siclari
Olimpia
O
Rossi
Giulio
G
Cittadini
Achille
A
D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D049030:Dystroglycans / Q000032:analysis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007558:Italy / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D016019:Survival Analysis
C483081:DAG1 protein, human; D009363:Neoplasm Proteins; D049030:Dystroglycans