Molecular tumor markers in the blood: early prediction of disease outcome in melanoma patients treated with a melanoma vaccine.
OBJECTIVE
Patients with American Joint Committee on Cancer (AJCC) stage III melanoma are at high risk of recurrence and death. We hypothesized that a multiple-marker reverse transcriptase polymerase chain reaction (MM-RT-PCR) blood assay could predict, early in the course of therapy, those patients destined to experience treatment failure with a melanoma vaccine (MV) previously shown to improve survival in a phase II clinical trial.


METHODS
After complete surgical resection, prospectively collected cryopreserved peripheral-blood lymphocyte specimens (n = 90) from the serial bleeds of 30 patients with AJCC stage III melanoma were studied by MM-RT-PCR, using the markers tyrosinase, melanoma antigen recognized by T cells-1 (MART-1), and universal melanoma antigen gene-A (uMAG-A). All patients were enrolled in a phase II MV trial during the period of blood draws, and were selected for this study in a blinded fashion. Median duration of clinical follow-up was 74 months for the 13 survivors and 11 months for the 17 nonsurvivors.


RESULTS
The presence of at least one melanoma-specific RT-PCR marker was associated with an increased risk of disease recurrence (risk rate, 3.12; P =.02) and decreased risk of survival (relative rate, 2.62; P =.0496) by multivariate analysis.


CONCLUSIONS
MM-RT-PCR of the blood provided early prediction of subsequent disease recurrence and death in clinically disease-free AJCC stage III melanoma patients enrolled in a MV phase II trial. On the basis of the results of this pilot study, the MM-RT-PCR blood assay should be considered as a clinically important monitoring tool for assessing patient response to adjuvant therapy, and in the surveillance of clinically disease-free patients for the earliest signs of recurrence.
Wascher
Robert A
RA
Department of Molecular Oncology, John Wayne Cancer Institute, Saint John's Health Center, Santa Monica, CA 90404, USA.
Morton
Donald L
DL
Kuo
Christine
C
Elashoff
Robert M
RM
Wang
He-Jing
HJ
Gerami
Mehri
M
Hoon
Dave S B
DS
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D019496:Cancer Vaccines / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D006801:Humans; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000473:pathology*; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000032:analysis; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000032:analysis; D009364:Neoplasm Recurrence, Local; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology*; D013534:Survival; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D014442:Monophenol Monooxygenase