Expression of cancer–testis antigens in endometrial carcinomas using a tissue microarray

Abstract

Cancer-testis (CT) antigens are expressed in a variety of malignant tumors, but in normal adult tissue, they are only expressed in testicular germ cells. Owing to this tumor-associated expression pattern, these antigens are of major interest as potential targets for immunotherapy and possibly for diagnostic purposes. This study was performed to analyze the expression of four CT antigens, NY-ESO-1, MAGE-A3, MAGE-A4, and CT7/MAGE-C1, in endometrial carcinoma using immunohistochemistry, and to correlate expression with histologic subtypes, grade, and expression of WT1 and p53. Formalin-fixed paraffin-embedded tissues of 130 endometrial carcinomas of the following types and grades were analyzed using a tissue microarray: 85 endometrioid carcinomas (FIGO grade 1, 39; grade 2, 11; and grade 3, 35), 18 papillary serous carcinomas, 12 clear cell carcinomas, 13 malignant mixed mullerian tumors, one mucinous adenocarcinoma, and one undifferentiated carcinoma. The following anti-CT monoclonal antibodies/antigens were studied by immunohistochemistry: monoclonal antibody ES121/NY-ESO-1, monoclonal antibody M3H67/MAGE-A3, monoclonal antibody 57B/ MAGE-A4, and monoclonal antibody CT7-33/CT7. The CT expression data were compared to WT1 and p53 protein expression as analyzed in a previous study. Positive staining with anti-CT monoclonal antibodies was graded as follows: focal, o5% positive cells; 1 þ , 5-25% cells; 2 þ , 26-50% cells; 3 þ , 51-75%; and 4 þ , 475% cells. The 3 þ and 4 þ staining patterns were considered homogeneous patterns of potential clinical significance and were scored positive for statistical analysis. In low-grade tumors, the most immunoreactivity was seen with mAb M3H67 but little labeling was observed with the other monoclonal antibodies. In high-grade tumors, monoclonal antibodies M3H67 (25%), 57B (23%), and CT7-33 (20%) showed the highest reactivity, while ES121 showed the lowest immunoreactivity (6%). The staining pattern was mostly heterogeneous. Statistical significance was found solely for the correlation of monoclonal antibody 57B staining and p53 expression. No correlation was found for any anti-CT monoclonal antibody staining and clinical stage or for anti-CT staining and WT1 expression. CT antigens CT7, MAGE-A3 and MAGE-A4, but not NY-ESO-1, are expressed in high-grade endometrial carcinomas, and expression of MAGE-A4 is correlated with the presence of overexpressed p53.

Global Expression Analysis of Cancer/Testis Genes in Uterine Cancers Reveals a High Incidence of BORIS Expression

“…This finding is in contrast to results obtained by Resnick et al who observed higher incidence of expression using immunohistochemistry (5). However, our data are in concordance with another report that found only 6% of endometrial cancers expressed NY-ESO-1, and 23% expressed MAGEA4 (6). We chose to re-evaluate NY-ESO-1 expression in our cancers by conventional nonquantitative reverse transcription-PCR.…”

“…Furthermore, PRAME was identified as a cancer biomarker based on its increased level of expression in a comparison of normal endometrium and endometrial cancer. 6 This expression in the most common histologic type of endometrial cancer deserves further investigation, including analysis of the relative levels of transcript and protein in normal and malignant uterine tissue. Recent progress in the understanding of the role of PRAME in modulating tumor progression through retinoic acid signaling further highlights the need for more study in this area (23).…”

“…Resnick et al examined the expression of MAGEA4 and NY-ESO-1 in a variety of uterine cancers and observed that a high proportion of uterine carcinosarcomas (91%) and papillary serous cancers (63%) expressed these antigens (5). In contrast Chitale et al evaluated NY-ESO-1 by immunohistochemistry and found that only 6% of endometrial carcinomas expressed the gene (6). Various other CT genes have been evaluated in endometrial cancers, including MAGEA4, MAGEA3, MAGE-C1 (CT7), SSX, and CAGE (6 -8).…”

BORIS, a paralogue of the transcription factor, CTCF, is aberrantly expressed in breast tumours

“…The function of the majority of the CTAs is still unknown; however, some CTAs are thought to be implicated in the regulation of gene expression and others may control gametogenesis (Old, 2001;Kalejs and Erenpreisa, 2005). The CTAs are attractive targets for developing cancer-specific immunotherapy because of their highly restricted expression in normal tissues and broad expression in a wide range of tumours (Chitale et al, 2005).…”

Expression of the melanoma-associated antigen is associated with progression of human thyroid cancer

“…Also referred to as 'cancer-testis antigens', they are not expressed in normal tissues except the testis and placenta. In neoplastic lesions, they have been found to be expressed in 12-60% of solid malignant tumors including lung (Fischer et al 1997, Jang et al 2001, liver (Kobayashi et al 2000), endometrial (Chitale et al 2005), and genitourinary carcinomas (Hudolin et al 2006, Picard et al 2007) and cholangiocarcinomas (Tsuneyama et al 2004).…”