What Is the Role of Sequential Reverse-Transcriptase Polymerase Chain Reaction Analysis of Melanoma-Specific mRNA in the Peripheral Blood of Melanoma Patients?

Abstract

TO THEEDITOR: WereadwithgreatinterestthearticlebyScoggins et al 1 that reports the results obtained by reverse-transcriptase polymerase chain reaction (RT-PCR) analysis of melanoma-specific mRNA detected on both sentinel lymph node (SLN) biopsies and peripheral blood mononuclear cells (PBMCs) in patients included in the Sunbelt Melanoma Trial. In particular, RT-PCR analyses using four markers (tyrosinase, MART1, MAGE3, and GP-100) were performed on PBMCs to detect occult melanoma cells in a very large number of patients (n 820) both at study entry and during follow-up (3 months after surgery and annually thereafter). The results appear to exclude a prognostic relevance of RT-PCR on peripheral blood. There were no differences in disease-free survival (DFS), distant disease-free survival, and overall survival (OS) rates when comparing patients with at least one positive marker at any time duringfollow-upandpatientswithmarkersthatwerealwaysnegative; only patients with more than one RT-PCR marker in the peripheral blood showed a significantly lower DFS and distant disease-free survival, but not OS, with respect to the others. Itwouldbeofgreatinterest,inouropinion,toevaluateRT-PCR resultsinperipheralbloodaccordingtothediseasestage,thusseparatingSLN-negativestageIIpatientsfromSLN-positivestageIIIpatients. Indeed, according to the data reported by Scoggins et al in their Table 2, 1 SLN status defined by using standard hematoxylin/eosin and immunohistochemistry is associated with significant differences in PBMC RT-PCR expression in as much as the percentage of SLNpositive patients was significantly higher in the RT-PCR‐positive group (36%) than in the RT-PCR‐negative group (24%; P .006). Actually, literature data failed to demonstrate a prognostic relevance of RT-PCR (tyrosinase in the majority of cases) in stage I-II patients. 2 Incontrast,themajorityofstudiesthatanalyzedtyrosinaseexpression intheperipheralbloodusingsequentialdeterminationsatsetintervals during the follow-up of stage III patients demonstrated by means of multivariate analysis that the finding of at least one RT-PCR tyrosinase-positive determination carries an adverse independent prognostic significance (reviewed in Quaglino et al 3 ). This is in contrast with the results obtained from single tyrosinase determination studies, the majority of which failed to demonstrate a prognostic significance of the RT-PCR assay. 4