Cancer/Testis (CT) Antigens Show Differential Expression in Seminomas and Non-Seminomatous Germ Cell Tumors.
Yao-Tseng Chen, Dengfeng Cao, Rita Chiu, Lloyd J Old. Weill Cornell Medical College, New York; Washington University School of Medicine, St. Louis; Ludwig Institute for Cancer Research, New York
Background: Cancer/testis (CT) antigens comprise a group of proteins that are normally only expressed in germ cells and yet are aberrantly activated in a wide variety of human cancers. In adult testis, many CT antigens show restricted expression in spermatogonia and primary spermatocytes. We recently showed that multiple CT antigens are expressed in fetal gonads, but only in germ cells that have lost the expression of OCT3/4, a pluripotent cell marker expressed in all seminoma and embryonal carcinoma, but not in other germ cell tumors.
Design: Expression of 7 CT antigens (MAGEA, NY-ESO-1, GAGE, CT7, CT10, CT45 and SAGE1) was evaluated immunohistochemically in 76 classical seminomas by tissue microarray and on whole sections on selected cases. Other germ cell tumors, including 24 embryonal carcinomas, 20 yolk sac tumors, 9 teratomas, 3 choriocarcinomas and 2 spematocytic seminomas, were evaluated using whole sections. Co-expression of OCT3/4 and CT antigens was evaluated by double staining of OCT3/4 and CT7 (or OCT3/4 and MAGEA).
Results: Classical seminomas expressed different CT antigens in highly variable frequencies, ranging from >80% (CT7, CT10, CT45 and GAGE), 63% (MAGEA), 18% (NY-ESO-1) to only 4% (SAGE1). Intratubular germ cell neoplasia (ITGCN), uniformly OCT3/4-positive, were almost always CT-negative, even in CT-positive classical seminomas. In comparison, both spermatocytic seminomas, including the intratubular growth component, showed diffuse strong expression of all 7 CT antigens. Non-seminomatous germ cell tumors expressed CT antigens much less frequently and often showed heterogeneous staining patterns in most cases. 21 of 24 embryonal carcinomas were either CT-negative (10 cases) or positive in <5% of the tumor cells (11 cases), and diffuse staining was observed in a single case. Similarly, teratomas were CT-negative (5/9) or minimally positive (4/9). Twelve of 20 yolk sac tumors and 2 of 3 choriocarcinomas expressed at least 1 CT antigen, but showed more focal staining than in seminomas.
Conclusions: Spermatocytic seminomas, originated from adult germ cells, retain their physiological expression of CT antigens. Classical seminomas, arising from prenatal gonocytes, show frequent CT antigen expression but not in ITGCN. Non-seminomatous germ cell tumors express CT antigens less frequently and often in small subsets of tumor cells. These differences likely reflect the different origin and differentiation states of the germ cell tumors.
Category: Genitourinary (including renal tumors)
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 84, Tuesday Afternoon