Expression of MAGE-A3, NY-ESO-1, LAGE-1 and PRAME in urothelial carcinoma

• Published in: British journal of cancer 2012-06, Vol.107 (1), p.116-122
• Main Authors: Dyrskjøt, L, Zieger, K, Kissow Lildal, T, Reinert, T, Gruselle, O, Coche, T, Borre, M, Ørntoft, T F
• Format: Article
• Language: English
• Subjects: 631/208/199; 692/699/67/1059/2325; 692/699/67/589/1336; Adult; Aged; Aged, 80 and over; Antigens; Antigens, Neoplasm - genetics; Antigens, Neoplasm - metabolism; Antigens, Surface - metabolism; Biomedical and Life Sciences; Biomedicine; Bladder cancer; Cancer Research; Chemotherapy; Disease-Free Survival; DNA Methylation; Drug Resistance; Epidemiology; Female; Gene Expression; Hospitals; Humans; Immunotherapy; Male; Medical prognosis; Medical research; Membrane Proteins - metabolism; Metastasis; Molecular Diagnostics; Molecular Medicine; Neoplasm Proteins - metabolism; Oncology; Patients; Prognosis; Tumors; Urinary Bladder Neoplasms - metabolism; Urological surgery; Vaccines
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2012.215

Background: The potential for cancer-testis (CT) antigens as targets for immunotherapy in cancer patients has been heavily investigated, and currently cancer vaccine trials based on the CT antigens, MAGE-A3 and NY-ESO-1, are being carried out. Methods: We used specific q-RT-PCR assays to analyse the expression of the CT genes MAGE-A3 , NY-ESO-1 ( CTAG1B ), LAGE-1 ( CTAG2 ) and PRAME in a panel of bladder tumours from 350 patients with long-term follow-up and detailed treatment information. Results: Overall, 43% of the tumours expressed MAGE-A3 , 35% expressed NY-ESO-1 , 27% expressed LAGE-1 and 20% expressed PRAME . In all, 56% of the tumours expressed at least one of the CT genes analysed. Univariate Cox regression analysis of CT gene expression in non-muscle-invasive tumours showed that expression of MAGE-A3 ( P =0.026), LAGE-1 ( P =0.001) and NY-ESO-1 ( P =0.040) was significantly associated with a shorter progression-free survival. In addition, we found that patients with tumours expressing PRAME responded poorly to chemotherapy ( P =0.02, χ 2 -test). Conclusion: Cancer-testis genes are frequently expressed in bladder cancer and especially in tumours of high stage and grade. In addition, the CT gene expression may have both prognostic and predictive value. Development of specific immunotherapy against the CT antigens in bladder cancer may ultimately increase patient survival.