High frequency of MAGE-A4 and MAGE-A9 expression in high-risk bladder cancer.
Cancer-testis (CT) genes encode proteins that are ideal targets for cancer immunotherapy because of their restricted expression in normal tissues and frequent expression in cancers. We previously observed that MAGE-A9 was one of the CT genes most frequently expressed in bladder tumors. To confirm that observation and evaluate the potential prognostic value of MAGE-A9 protein, we analyzed its expression by immunohistochemistry in 493 primary bladder tumors and 33 lymph node metastases, in comparison with MAGE-A4 protein, also frequently expressed in bladder tumors. Overall, MAGE-A4 and MAGE-A9 were observed, respectively, in 38% and 63% of nonmuscle-invasive tumors, 48% and 57% of muscle-invasive tumors, 65% and 84% of carcinomas in situ and in 73% and 85% of lymph node metastases. Expression was associated with higher grade (MAGE-A4, p = 0.007; MAGE-A9, p = 0.012). In multivariate Cox regression analyses, expression of MAGE-A9 in pTa tumors was associated with recurrence (HR = 1.829; p = 0.010). In univariate analyses, MAGE-A4 expression in these same tumors was associated with progression to muscle-invasive cancer (HR = 7.417, p = 0.013). MAGE-A9 expression was even more predictive of progression as all tumors that progressed expressed this antigen. In muscle-invasive bladder tumors, no association was found between expression of either MAGE and bladder cancer-specific death. In conclusion, MAGE-A9 is a target of choice for bladder cancer immunotherapy as it is expressed in 60% of bladder tumors, predominantly high-grade tumors, and at higher frequency in pTis and metastatic tumors. Moreover, in pTa tumors, an immunotherapy targeting MAGE-A9 could be protective against recurrence and progression to more advanced cancer.
Bergeron
Alain
A
Centre de recherche en cancérologie de l'Université Laval, L'Hôtel-Dieu de Québec, Centre Hospitalier Universitaire de Québec, Québec, Canada.
Picard
Valérie
V
LaRue
Hélène
H
Harel
Francois
F
Hovington
Hélène
H
Lacombe
Louis
L
Fradet
Yves
Y
D000951:Antigens, Neoplasm / Q000378:metabolism*; D015331:Cohort Studies; D006801:Humans; D008207:Lymphatic Metastasis; D019042:Muscle Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
D000951:Antigens, Neoplasm; C095204:MAGEA4 protein, human; C520253:MAGEA9 protein, human; D009363:Neoplasm Proteins