Tyrosinase mRNA in blood of patients with melanoma treated with adjuvant interferon.
OBJECTIVE
To evaluate the clinical significance of the detection of circulating melanoma cells in patients treated with adjuvant interferon and to determine their potential value as a marker of interferon response.


METHODS
We prospectively analyzed 616 peripheral-blood samples from 120 melanoma patients with stage IIA (n = 33), IIB (n = 22), III (n = 50), or IV (surgically resected) (n = 15) disease receiving adjuvant interferon alfa-2b therapy. Tyrosinase mRNA was assayed by reverse transcriptase polymerase chain reaction (RT-PCR) as a marker of circulating melanoma cells before the start of interferon and every 2 to 3 months thereafter.


RESULTS
With a median follow-up time of 32.3 months (range, 7.1 to 77.5 months), 47 patients (39.8%) relapsed and 31 (26%) died. During adjuvant interferon treatment, 76 patients (64%) had undetected circulating melanoma cells and 44 patients (36%) had a positive RT-PCR result in at least one sample. Actuarial 5-year disease-free survival was 62% in patients with persistently negative RT-PCR during interferon treatment and 38% for patients with positive RT-PCR during interferon (P =.02). Actuarial 5-year overall survival was 75% and 50%, respectively (P =.03).


CONCLUSIONS
Patients with melanoma and tyrosinase mRNA detected in the blood during adjuvant interferon therapy had a worse prognosis compared with patients with undetected tyrosinase mRNA during treatment. Further investigation into the detection of circulating melanoma cells as a surrogate marker of response to adjuvant interferon therapy is warranted.
D000206:Actuarial Analysis; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000188:drug therapy; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000097:blood*; D009360:Neoplastic Cells, Circulating; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood*; D012334:RNA, Neoplasm / Q000097:blood*; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000097:blood* / Q000188:drug therapy
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D014442:Monophenol Monooxygenase