Chromosome X-encoded Cancer/Testis antigens are less frequently expressed in non-seminomatous germ cell tumors than in seminomas

Cancer/Testis (CT) antigens are normally only expressed in germ cells and yet are aberrantly activated in a wide variety of human cancers. Most chromosome X-encoded CT antigens (CT-X) show restricted expression in pre-meiotic germ cells in adult testis, except for the expression of SPANX in post-meiotic germ cells. In the present study, the expression of eight CT-X antigens (MAGE-A, NY-ESO-1, GAGE, MAGE-C1/CT7, MAGE-C2/CT10, CT45, SAGE1, and SPANX) in non-seminomatous germ cell tumors was evaluated immunohistochemically, including 24 embryonal carcinomas, 20 yolk sac tumors, 9 teratomas, and 3 choriocarcinomas, and the results were compared to our previous study of 77 classic seminomas and 2 spermatocytic seminomas. SPANX was not detected in any germ cell tumors tested. Spermatocytic seminoma showed strong expression of all CT-X antigens tested (except SPANX), reflecting their origin from adult CT-Xpositive pre-meiotic germ cells. Classic seminomas, originating from prenatal gonocytes, showed widely variable frequency of CT-X antigen expression, ranging from > 80% (CT7, CT10, CT45, and GAGE), 63% (MAGE-A), 18% (NY-ESO-1) to only 4% (SAGE1). In comparison, non-seminomatous germ cell tumors expressed CT-X antigens much less frequently and usually only in small subsets of tumor cells. Intratubular germ cell neoplasia (ITGCN) were mostly CT-X-negative, even in CT-X positive classic seminomas. These findings indicate that CT-X antigens are not expressed in the fetal precursor cells for germ cell tumors, and their expression likely reflects germ cell differentiation of the neoplastic cells (in seminomas) or aberrant gene activation as cancer antigens (in non-seminomatous tumors).