MAGE-A4, a germ cell specific marker, is expressed differentially in testicular tumors

BACKGROUND. Testicular germ cell tumors are the most common malignancy in y oung males, and the frequency of these tumors has risen dramatically over t he last century. Because it is known that the MAGE genes are expressed in a wide variety of tumors but are express ed only in the mitotic spermatogoni a (germ cells) and in the primary spermatocytes in the normal testis, the a uthors screened the expression of MAGE-A4 in a panel of testicular germ cel l tumors. METHODS. Monoclonal antibody 57B raised against MAGE-A4 was tested immunohi stochemically on 12 classical seminomas, 5 anaplastic seminomas, 10 various specimens of nonseminomatous germ cell tumors (NSGCTs), 2 combined tumors containing seminoma components, 1 Sertoli cell tumor, 2 Leydig cell tumors, and 15 carcinomas in situ (CIS). In addition, monoclonal antibody 57B was tested on embryonic gonad (age 8 weeks) and fetal gonads (ages 15 weeks, 17 weeks, and 28 weeks). RESULTS. Classical seminomas uniformly and specifically expressed MAGE-A4 c ompared with anaplastic seminomas and NSGCTs, which were negative for this antigen. Specific expression of MAGE-A4 also was seen in subpopulations of CIS cells, providing additional evidence for heterogeneity of the phenotype of these cells, in which it is I believed that differentiation and prolife ration generate seminomas and NSGCTs. Finally, MAGE-A4 was expressed in the fetal precursors of the stem germ cells from 17 weeks of gestation onward, in accordance the fact that CIS can arise from prespermatogonia in the fet us. CONCLUSIONS. MAGE-A4 can be considered a potential specific marker for norm al premeiotic germ cells and germ cell tumors and can be used to characteri ze classical seminomas. Cancer, 2001;92:2778-85. (C) 2001 American Cancer S ociety.