MART-1 is expressed less frequently on circulating melanoma cells in patients who develop distant compared with locoregional metastases.
OBJECTIVE
Polymerase chain reaction (PCR) with tyrosinase and with MART-1 permits detection of small numbers of circulating melanoma cells (CMCs) in patients who have undergone surgical resection of localized disease. In a previous study, we showed that PCR with MART-1 had sensitivity and specificity similar to those of PCR with tyrosinase in terms of detection of CMCs but that PCR with MART-1 seemed to identify a different but overlapping subgroup of patients. In the current study, we examined the utility and prognostic significance of PCR with tyrosinase and with MART-1.


METHODS
We analyzed the prognostic significance of the patterns of expression of tyrosinase and MART-1 in 186 patients followed sequentially before and after surgical removal of American Joint Committee on Cancer stage I, II, or III melanoma.


RESULTS
PCR with tyrosinase and with MART-1 in the first 3 months after surgery identified 68.5% of 73 patients who developed recurrence in the 2-year period after surgery. Approximately 35% of patients with positive tests remained disease-free at 2-year follow-up. We found that patients with disseminated recurrence had a significantly lower incidence of MART-1-positive CMCs (16%) than of tyrosinase-positive CMCs (63%). Patients with locoregional metastases had CMCs that expressed tyrosinase and MART-1 at similar rates. These differences in expression of the markers in patients with disseminated recurrence were also associated with a much lower disease-free survival, in those who had CMCs that were positive for tyrosinase but negative for MART-1. The reverse applied in those with locoregional disease.


CONCLUSIONS
These findings suggest that PCR with MART-1 and with tyrosinase identifies subgroups of patients who develop disseminated or locally recurrent metastases. We hypothesize that immune responses against MART-1 may reduce the establishment of disseminated metastases.
Curry
B J
BJ
Oncology and Immunology Unit, Mater Misericordiae Hospital, Newcastle, and Sydney Melanoma Unit, Sydney, New South Wales, Australia.
Myers
K
K
Hersey
P
P
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000473:pathology* / Q000601:surgery; D014442:Monophenol Monooxygenase; D009363:Neoplasm Proteins; D009364:Neoplasm Recurrence, Local / Q000097:blood; D009360:Neoplastic Cells, Circulating; D011184:Postoperative Period; D011379:Prognosis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D014442:Monophenol Monooxygenase