Prospective multi-institutional study of reverse transcriptase polymerase chain reaction for molecular staging of melanoma.
OBJECTIVE
To evaluate the prognostic significance of molecular staging using reverse transcriptase polymerase chain reaction (RT-PCR) in detecting occult melanoma cells in sentinel lymph nodes (SLNs) and circulating bloodstream.


METHODS
In this multicenter study, eligibility criteria included patient age 18 to 71 years, invasive melanoma > or = 1.0 mm Breslow thickness, and no clinical evidence of metastasis. SLN biopsy and wide excision of the primary tumor were performed. SLNs were examined by serial-section histopathology and S-100 immunohistochemistry. A portion of each SLN was frozen for RT-PCR. In addition, RT-PCR was performed on peripheral-blood mononuclear cells (PBMCs). RT-PCR analysis was performed using four markers: tyrosinase, MART1, MAGE3, and GP-100. Disease-free survival (DFS), distant-DFS (DDFS), and overall survival (OS) were analyzed.


RESULTS
A total of 1,446 patients with histologically negative SLNs underwent RT-PCR analysis. At a median follow-up of 30 months, there was no difference in DFS, DDFS, or OS between the RT-PCR-positive (n = 620) and RT-PCR-negative (n = 826) patients. Analysis of PBMC from 820 patients revealed significant differences in DFS and DDFS, but not OS, for patients with detection of more than one RT-PCR marker in peripheral blood.


CONCLUSIONS
In this large, prospective, multi-institutional study, RT-PCR analysis on SLNs and PBMCs provides no additional prognostic information beyond standard histopathologic analysis of SLNs. Detection of more than one marker in PBMC is associated with a worse prognosis. RT-PCR remains investigational and should not be used to direct adjuvant therapy at this time.
Scoggins
Charles R
CR
Division of Surgical Oncology, Department of Surgery, University of Louisville, James Graham Brown Cancer Center and Center for Advanced Surgical Technologies (CAST), Louisville, KY 40292, USA.
Ross
Merrick I
MI
Reintgen
Douglas S
DS
Noyes
R Dirk
RD
Goydos
James S
JS
Beitsch
Peter D
PD
Urist
Marshall M
MM
Ariyan
Stephan
S
Davidson
B Scott
BS
Sussman
Jeffrey J
JJ
Edwards
Michael J
MJ
Martin
Robert C G
RC
Lewis
Angela M
AM
Stromberg
Arnold J
AJ
Conrad
Andrew J
AJ
Hagendoorn
Lee
L
Albrecht
Jeffrey
J
McMasters
Kelly M
KM
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D008207:Lymphatic Metastasis; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000473:pathology* / Q000601:surgery; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000032:analysis; D009363:Neoplasm Proteins / Q000032:analysis*; D009367:Neoplasm Staging / Q000379:methods*; D009360:Neoplastic Cells, Circulating; D011379:Prognosis; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000473:pathology* / Q000601:surgery; D016019:Survival Analysis; D058951:gp100 Melanoma Antigen
D000951:Antigens, Neoplasm; C072013:MAGEA3 protein, human; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D058951:gp100 Melanoma Antigen; D014442:Monophenol Monooxygenase