Cancer/testis antigen CT45: analysis of mRNA and protein expression in human cancer.
CT45 is a cancer/testis gene that we previously identified by massively parallel signature sequencing. Encoded by a multigene family on chromosome X, CT45 showed restricted mRNA expression to normal testis and various cancers. In this study, monoclonal antibodies were generated against recombinant CT45 protein, and CT45 protein expression in normal and tumor tissues was evaluated by immunohistochemical analysis. In adult normal tissue, CT45 expression was restricted to testicular germ cells, detected as a nuclear protein mainly at the stage of primary spermatocytes. In tumors, CT45 protein expression correlated with the mRNA levels detected by quantitative RT-PCR, and most lung cancer and ovarian cancers with CT45 mRNA at levels >1% of testicular expression were CT45 protein-positive. In positive cases, CT45 showed expression patterns that ranged from diffuse strong staining to heterogeneous and patchy expression. In lung cancer, CT45 expression was least frequent in adenocarcinoma, more frequent in squamous cell carcinoma and neuroendocrine tumors. Using tissue microarrays, 376 lung cancer, 219 ovarian cancer and 155 breast cancer were evaluated for CT45 protein expression. The expression frequency was highest in ovarian cancer (37%), followed by lung cancer (13%) and lowest in breast cancer (<5%). Given the focal nature of CT45 expression in many cases, these numbers represented the minimal frequency of expression in these tumor types. In summary, the expression frequency and characteristics of CT45 expression are similar to other CT cancer vaccine targets currently in clinical trials, e.g., NY-ESO-1 and MAGE-A, suggesting CT45 as a potentially useful cancer target.
Chen
Yao-Tseng
YT
Departments of Pathology and Surgery, Weill Cornell Medical College, New York, NY 10065, USA. ytchen@med.cornell.edu
Hsu
Melinda
M
Lee
Peishan
P
Shin
Sandra J
SJ
Mhawech-Fauceglia
Paulette
P
Odunsi
Kunle
K
Altorki
Nasser K
NK
Song
Chao-Jun
CJ
Jin
Bo-Quan
BQ
Simpson
Andrew J
AJ
Old
Lloyd J
LJ
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C502804:CT45A1 protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins