Expression and significance of cancer testis antigens in primary mucosal melanoma of the head and neck.
BACKGROUND
Cancer testis antigens (CTAs) are T-cell-defined tumor-associated antigens encoded by the genes and gene families such as MAGE, NY-ESO-1, and others. Their expression in a wide variety of malignant neoplasms but absence in all normal adult tissue except testicular germ cells makes them attractive targets for immunotherapy of cancer. Primary mucosal melanomas of the head and neck (HNMM) are rare aggressive malignant tumors that are usually difficult to treat. CTAs may provide useful targets for therapy; however, their expression in HNMM is not known.


METHODS
We analyzed 40 initial, 15 recurrent, and 15 metastatic HNMM to nonmucosal locations from 64 patients (oral, n = 30; sinonasal, n = 34). Immunohistochemistry was performed on archival tissue with monoclonal antibodies 57B, CT7-33, and ES121 to the following CTAs: MAGE-A4, CT7 (MAGE-C1), and NY-ESO-1, respectively.


RESULTS
CT7, MAGE-A4, and NY-ESO-1 expression was seen in 73%, 61%, and 24% of tumors, respectively, with 81% of the tumors expressing at least one of the CTAs. CT7 and MAGE-A4 were significantly more frequently expressed in tumors composed of epithelioid cells than spindle cells (p = .05). CTA expression did not correlate with disease progression, overall survival, and disease-specific survival.


CONCLUSIONS
CT7, MAGEA4, and NY-ESO-1 are frequently expressed in HNMM and may be potential targets for CTA-based immunotherapy. The expression does not seem to have prognostic significance.
Prasad
Manju L
ML
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. prasad-1@medctr.osu.edu
Jungbluth
Achim A
AA
Patel
Snehal G
SG
Iversen
Kristin
K
Hoshaw-Woodard
Stacy
S
Busam
Klaus J
KJ
D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011336:Probability; D011379:Prognosis; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016019:Survival Analysis
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C473332:CT7 antigen, human; C104948:CTAG1B protein, human; C110905:MAGEC1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins