Tumor antigen expression in melanoma varies according to antigen and stage.
OBJECTIVE
Melanoma cells express antigens that can induce T-cell and antibody responses. Obtaining a detailed understanding of antigen expression in primary and metastatic melanoma is essential if these molecules are to be useful targets for immunotherapy of melanoma.


METHODS
Malignant melanomas (n = 586) from 426 patients were typed for antigen expression. Multiple samples were available from 86 individuals, enabling analysis of antigen expression patterns over time. Paraffin-embedded samples were tested by immunohistochemistry for the presence of the differentiation antigens: gp100, Melan-A, tyrosinase, and the "cancer/testis" antigens MAGE-A1, MAGE-A4, and NY-ESO-1.


RESULTS
Samples were primary tumors (n = 251), lymph node metastases (n = 174), s.c. metastases (n = 71), and distant metastases (n = 90). The differentiation antigens were strongly expressed in 93% to 95% of tumors regardless of stage. In contrast, the frequency of cancer/testis antigen expression in primary tumors for MAGE-A1, MAGE-A4, and NY-ESO-1 was lower (20%, 9%, and 45%, respectively). MAGE-A1 and MAGE-A4 were acquired with advancing disease (to 51% and 44% in distant metastases, respectively) but not NY-ESO-1, which remained positive in 45%. MAGE-A1 expression was twice as prevalent in ulcerated primaries as in nonulcerated primaries (30% versus 15%; P = 0.006) and in thicker as opposed to thin melanomas (26% versus 10%; P = 0.1).


CONCLUSIONS
This large series describes patterns of antigen expression in melanoma and their evolution over time. This will help inform decisions about selection of patients and target antigens for melanoma immunotherapy clinical trials.
Barrow
Catherine
C
Ludwig Institute for Cancer Research, Melbourne, Australia.
Browning
Judy
J
MacGregor
Duncan
D
Davis
Ian D
ID
Sturrock
Sue
S
Jungbluth
Achim A
AA
Cebon
Jonathan
J
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000032:analysis / Q000235:genetics / Q000276:immunology; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D009367:Neoplasm Staging
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor