Molecular upstaging based on paraffin-embedded sentinel lymph nodes: ten-year follow-up confirms prognostic utility in melanoma patients.
OBJECTIVE
To determine the long-term clinical significance of molecular upstaging in histopathology-negative, paraffin-embedded (PE) sentinel lymph nodes (SLNs) from melanoma patients.


BACKGROUND
Histopathologic evaluation can miss clinically relevant melanoma micrometastases in SLNs. This longitudinal correlative study is the first 10-year prognostic evaluation of a multimarker quantitative real-time reverse transcriptase-polymerase chain reaction (qRT) assay for PE melanoma-draining SLNs.


METHODS
The SLN sections (n = 214) were assessed by qRT assay for 4 established messenger RNA biomarkers: MART-1, MAGE-A3, GalNAc-T, and PAX3.


RESULTS
The qRT assay upstaged 48 of 161 histopathology-negative (hematoxylin-eosin and immunohistochemistry) SLN specimens. At a median follow-up of 11.3 years for the entire cohort, estimated rates of 10-year overall survival (OS) and melanoma-specific survival (MSS) were 82% and 94%, respectively, for histopathology-negative/qRT-negative patients; 56% and 61%, respectively, for histopathology-positive patients; and 52% and 60%, respectively, for histopathology-negative/qRT-positive patients (P < 0.001 for OS, P < 0.001 for MSS). In a multivariate analysis of known melanoma prognostic factors, qRT positivity was significant (P < 0.05) for disease-free survival (hazard ratio [HR], 4.3; 95% confidence interval (CI), 2.3-7.8), distant disease-free survival (HR, 6.6; 95% CI, 2.9-14.6), MSS (HR, 6.2; 95% CI, 2.6-14.4), and OS (HR, 2.8; 95% CI, 1.6-4.9).


CONCLUSIONS
The multimarker qRT assay has prognostic significance for molecular upstaging of PE melanoma-draining SLNs. Molecular upstaging of histopathology-negative SLNs confers a prognosis similar to that associated with SLN micrometastasis, and the number of positive qRT biomarkers is correlated to disease outcome.
Department of Molecular Oncology, Santa Monica, CA, USA.
Michael B
MB
Nicholl
David
D
Elashoff
Hiroya
H
Takeuchi
Donald L
DL
Morton
Dave S B
DS
Hoon
D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D058965:MART-1 Antigen / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000556:secondary* / Q000601:surgery; D008875:Middle Aged; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016612:Paraffin Embedding; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D016019:Survival Analysis; D000097763:Polypeptide N-acetylgalactosaminyltransferase
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D058965:MART-1 Antigen; D017350:N-Acetylgalactosaminyltransferases; D009363:Neoplasm Proteins; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C072013:MAGEA3 protein, human; C489409:PAX3 protein, human