title: MAGE-A is More Highly Expressed Than NY-ESO-1 in a Systematic Immunohistochemical Analysis of 3668 Cases.
abstract: Two cancer testis antigens, the New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and the melanoma-antigen family A (MAGE-A), represent promising immunotherapy targets due to the low expression of these antigens in nonmalignant tissue. To assess overexpression patterns in various cancers, we performed a systematic immunohistochemical analysis for NY-ESO-1 and MAGE-A on tissue array samples of 3668 common epithelial carcinomas (CA) and germ cell tumors of high prevalence and mortality. Here, we find significantly higher expression of MAGE-A (>50% on tumor cells) compared with NY-ESO-1 in several CAs including cutaneous squamous cell carcinomas (SCC) (52.8%/2.8%), esophageal SCC (50%/0%), head and neck SCC (41.1%/<1%), bladder urothelial CA (40.4%/8.3%), cervical/anal SCC (37.5%/0%), lung SCC (34%/3.8%), lung adenocarcinomas (27.6%/3.9%), ovarian CA (26.4%/3.6%), endometrial CA (26.3%/1.3%), lung small cell CA (24.4%/2.4%), gastric adenocarcinomas (20%/4%), breast mucinous CA (19.3%/0%), hepatocellular CA (18.8%/1.2%), breast infiltrating ductal CA (16.4%/1.8%), colorectal adenocarcinomas (10.7%/<1%), cholangiocarcinomas (9.8%/0%), thymic CA (9%/4.5%), and mesotheliomas (7.9%/<1%). Furthermore, high expression of MAGE-A, but not NY-ESO-1, was seen in whole slide evaluations of an independent cohort of metastatic SCC (45.5%/3.6%) and metastatic CA (13.5%/0%) of various primaries with significantly higher expression of MAGE-A in metastatic SCC compared with other metastatic CA. MAGE-A is also more highly expressed in germ cell tumors, seminomas (69%/3.5%) and nonseminomas (40.1%/4.7%). In summary, MAGE-A is more highly expressed than NY-ESO-1 in a majority of human malignancies, and targeting MAGE-A may benefit a large number of patients.
authors.affiliation: *Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN †Laboratory of Pathology ‡Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Sid P
authors.initials: SP
authors.lastname: Kerkar
authors.forename: Zeng-Feng
authors.initials: ZF
authors.lastname: Wang
authors.forename: Jerzy
authors.initials: J
authors.lastname: Lasota
authors.forename: Tristen
authors.initials: T
authors.lastname: Park
authors.forename: Krishna
authors.initials: K
authors.lastname: Patel
authors.forename: Eric
authors.initials: E
authors.lastname: Groh
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: Markku M
authors.initials: MM
authors.lastname: Miettinen
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D058950:Melanoma-Specific Antigens / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009373:Neoplasms, Germ Cell and Embryonal / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; C072011:MAGEA1 protein, human; D058950:Melanoma-Specific Antigens; D008565:Membrane Proteins