Tyrosinase mRNA in blood of patients with melanoma treated with adjuvant interferon

J Clin Oncol. 2002 Oct 1;20(19):4032-9. doi: 10.1200/JCO.2002.08.009.

Abstract

Purpose: 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.

Patients and 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actuarial Analysis
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / blood
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Female
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Male
  • Melanoma / blood*
  • Melanoma / drug therapy
  • Middle Aged
  • Monophenol Monooxygenase / blood*
  • Neoplastic Cells, Circulating
  • Prospective Studies
  • RNA, Messenger / blood*
  • RNA, Neoplasm / blood*
  • Recombinant Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin Neoplasms / blood*
  • Skin Neoplasms / drug therapy

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Interferon alpha-2
  • Interferon-alpha
  • RNA, Messenger
  • RNA, Neoplasm
  • Recombinant Proteins
  • Monophenol Monooxygenase