Prediction of disease outcome in melanoma patients by molecular analysis of paraffin-embedded sentinel lymph nodes.
OBJECTIVE
A significant number of patients who develop recurrence after a histopathologically negative sentinel lymph node (SLN) biopsy will demonstrate occult metastases on re-evaluation of the SLNs with serial sectioning and immunohistochemistry. Reverse transcriptase polymerase chain reaction (RT-PCR) has been evaluated to improve disease staging and avoid false-negative findings in fresh or frozen-section SLNs. The purpose of this study was to develop a multimarker RT-PCR assay for assessing melanoma patients' archived paraffin-embedded (PE) SLNs.


METHODS
Archived PE histopathologically positive (n = 37) and negative (n = 40) SLNs from patients with primary melanoma were analyzed using a semiquantitative multimarker RT-PCR assay.


RESULTS
Marker expression in histopathologically positive and negative SLNs were as follows: 89%, 92%, 35%, and 43% (positive) and 40%, 33%, 5%, and 13% (negative) for tyrosinase, melanoma antigen recognized by T cells-1, tyrosinase-related protein-1, and tyrosinase-related protein-2, respectively. Twenty-five percent of histopathologically negative SLN patients were upstaged using at least two markers. Of these, 80% developed a recurrence. Furthermore, at a median follow-up of 55 months, patients with histopathologically negative SLNs who expressed zero or one marker had a significantly improved disease-free (P <.002) and overall (P <.03) survival versus those expressing two or more markers.


CONCLUSIONS
These findings demonstrate the feasibility of a multimarker RT-PCR assay for evaluating archived PE SLNs. More significantly, identification of molecular risk factors can be detected in histopathologically negative SLNs for distinguishing early-stage melanoma patients with a worse prognosis.
Kuo
Christine T
CT
Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Blvd, Santa Monica, CA 90404, USA.
Hoon
Dave S B
DS
Takeuchi
Hiroya
H
Turner
Roderick
R
Wang
He-Jing
HJ
Morton
Donald L
DL
Taback
Bret
B
D000328:Adult; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011237:Predictive Value of Tests; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D013048:Specimen Handling; D016896:Treatment Outcome
D005819:Genetic Markers