Tissue microarray evaluation of Melanoma antigen E (MAGE) tumor-associated antigen expression: potential indications for specific immunotherapy and prognostic relevance in squamous cell lung carcinoma.
OBJECTIVE
To evaluate MAGE tumor-associated antigen (TAA) expression in an extensive panel of normal and neoplastic tissues.


BACKGROUND
TAAs of the MAGE family represent targets of active specific immunotherapy. Limited-size studies indicate that they are expressed in normal testis and tumors of different histologies. High-throughput tissue microarray (TMA) technology and MAGE TAA-specific monoclonal antibodies now allow us to comprehensively evaluate their expression in large numbers of tissues and to address clinical correlations.


METHODS
A TMA containing 3,520 samples from 197 different tissues and a non-small-cell lung cancer TMA including 301 specimens were stained using the MAGE TAA-specific monoclonal antibody 57B. For patients with squamous cell carcinoma of the lung, the dichotomous result (positive vs. negative) of MAGE TAA staining was used as a predictor variable along with other covariates in proportional hazard regression analysis of tumor-specific survival.


RESULTS
MAGE TAAs are expressed with frequencies ranging between 22.7% (larynx) and 50% of cases (lung) in squamous cell carcinomas from different anatomic areas and in large cell carcinomas of the lung (37.9%). The authors provide here the first description of MAGE TAA expression in basalioma (48.1%). To investigate the clinical significance of MAGE expression in a frequently positive tumor type, a non-small-cell lung cancer, TMA was then studied. In this TMA 43.2% of tumors were 57B positive. In patients with squamous cell carcinoma, MAGE TAA positivity was significantly correlated with a shorter tumor-specific survival in the proportional hazard regression analysis model.


CONCLUSIONS
These data suggest novel potential therapeutic indications in different types of cancers. In lung squamous cell carcinoma, the significant association of MAGE TAA expression with poor prognosis suggests that patients with 57B-positive tumors may benefit from early, specific immunotherapy procedures.
Bolli
Martin
M
Department of Surgery, University Hospital, Basel, Switzerland. mbolli@uhbs.ch
Kocher
Thomas
T
Adamina
Michel
M
Guller
Ulrich
U
Dalquen
Peter
P
Haas
Philippe
P
Mirlacher
Martina
M
Gambazzi
Franco
F
Harder
Felix
F
Heberer
Michael
M
Sauter
Guido
G
Spagnoli
Giulio C
GC
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000951:Antigens, Neoplasm / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis; D001707:Biopsy, Needle; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D016009:Chi-Square Distribution; D046508:Culture Techniques; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012016:Reference Values; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins