title: Prognostic relevance of MAGE-A4 tumor antigen expression in transitional cell carcinoma of the urinary bladder: a tissue microarray study.
abstract: TAAs of the MAGE family are mostly studied as targets of specific immune responses. Their potential relevance as tumor markers has also been underlined. We used a MAb, 57B, recognizing MAGE-A4 protein in paraffin-embedded sections, to evaluate its expression in bladder cancers by employing TMA including 2,317 samples from 1,849 patients. In 2,090/2,317 cases (90.2%), immunostaining yielded interpretable results. Since for some patients more than 1 sample was available, only interpretable first biopsies (n = 1,628) were considered. MAGE-A4 protein was expressed at significantly (p < 0.001) higher frequency in squamous (25/55, 45.5%) than in adeno (4/15, 26.7%), sarcomatoid (4/14, 28.6%), small cell (5/20, 25%) or transitional cell (281/1,522, 18.5%) carcinomas. In TCCs, overall MAGE-A4 positivity was significantly correlated with invasive phenotype (p < 0.001) and high tumor grade (p < 0.0001). Clinical data from 908 TCC patients were retrospectively evaluated, revealing that strong 57B staining was highly significantly associated with decreased tumor-specific survival (p < 0.0001). These data suggest that evaluation of MAGE-A4 protein expression is useful in the identification of groups of TCCs characterized by severe prognosis, thus possibly providing indications for early MAGE TAA-targeted immunotherapy.
authors.affiliation: General Surgery Service, Department of Surgery, University Hospital of Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kocher
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.forename: Martin
authors.initials: M
authors.lastname: Bolli
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Thomas
authors.initials: T
authors.lastname: Forster
authors.forename: Elke
authors.initials: E
authors.lastname: Schultz-Thater
authors.forename: Eugenia
authors.initials: E
authors.lastname: Remmel
authors.forename: Christoph
authors.initials: C
authors.lastname: Noppen
authors.forename: Ulrico
authors.initials: U
authors.lastname: Schmid
authors.forename: Daniel
authors.initials: D
authors.lastname: Ackermann
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mihatsch
authors.forename: Thomas
authors.initials: T
authors.lastname: Gasser
authors.forename: Michael
authors.initials: M
authors.lastname: Heberer
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Giulio C
authors.initials: GC
authors.lastname: Spagnoli
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D000939:Epitopes; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011379:Prognosis; D013997:Time Factors; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000939:Epitopes; C095204:MAGEA4 protein, human; D009363:Neoplasm Proteins