Prognostic significance of the sequential detection of circulating melanoma cells by RT–PCR in high-risk melanoma patients receiving adjuvant interferon
BACKGROUND AND DESIGN Polymerase chain reaction (PCR) detection of circulating tumor cells from malignant melanoma (MM) was recently described, but the prognostic value of this method in the treatment of patients with MM remained unclear. In the present prospective study, blood samples (n = 193) were collected from 93 patients with MM: 10 stage I patients after primary tumor resection, 18 patients with regional lymph node metastases before node resection, 33 disease-free but high-risk patients (previously treated for node metastases), and 32 patients with distant metastases. Circulating melanocytes were detected using a reverse transcriptase PCR method that analyzes tyrosinase gene expression. All patients were kept under regular surveillance. RESULTS The PCR assay was always negative in normal individuals and in subjects with non-MM metastatic cancer, while it was positive in 16 of 32 patients with disseminated MM. Five of eight patients who were PCR-positive before node dissection vs one of 10 who were PCR-negative relapsed within 6 months after surgery. In high-risk but apparently disease-free patients, the risk of relapse within the next 6 months was 3.8 times higher after a positive test result. In patients with distant metastases, a positive PCR predicted rapid disease progression. CONCLUSIONS These data suggest that PCR detection of circulating melanocytes can be considered as a marker for rapid postoperative relapse after node dissection in patients with MM with regional node metastases, for short-term relapse in high-risk disease-free patients, and for rapid and severe progression in patients with distant metastases. This test may have a crucial interest in the treatment of patients with MM.