Expression of cancer-testis antigens in endometrial carcinomas using a tissue microarray.
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, <5% positive cells; 1+, 5-25% cells; 2+, 26-50% cells; 3+, 51-75%; and 4+, >75% cells. The 3+ and 4+ 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.
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Dhananjay A
DA
Chitale
Achim A
AA
Jungbluth
David S
DS
Marshall
Mario M
MM
Leitao
Cyrus V
CV
Hedvat
Denise
D
Kolb
Giulio C
GC
Spagnoli
Kristin
K
Iversen
Robert A
RA
Soslow
D018262:Adenocarcinoma, Clear Cell / Q000276:immunology / Q000473:pathology; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D002291:Carcinoma, Papillary / Q000276:immunology / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000276:immunology / Q000473:pathology; D016889:Endometrial Neoplasms / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D018200:Mixed Tumor, Mullerian / Q000276:immunology / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis; D013737:Testis / Q000276:immunology; D046888:Tissue Array Analysis / Q000379:methods*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D025721:WT1 Proteins / Q000096:biosynthesis
D000951:Antigens, Neoplasm; C473332:CT7 antigen, human; C104948:CTAG1B protein, human; C072013:MAGEA3 protein, human; C095204:MAGEA4 protein, human; C110905:MAGEC1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D025721:WT1 Proteins