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Prognostic Significance of Molecular Staging Study of Sentinel Lymph Nodes by Reverse Transcriptase-Polymerase Chain Reaction for Tyrosinase in Melanoma Patients

¹ Department of Dermatology, Hospital Universitario Germans Trias i Pujol, Carretera Canyet s/n. 08916-Badalona, Spain
² Department of Pathology, Hospital Universitario Germans Trias i Pujol, Universidad Autónoma de Barcelona, Carretera Canyet s/n. 08916-Badalona, Spain
³ Department of Nuclear Medicine, Hospital Universitario Germans Trias i Pujol, Universidad Autónoma de Barcelona, Carretera Canyet s/n. 08916-Badalona, Spain
⁴ Department of Surgery, Hospital Universitario Germans Trias i Pujol, Universidad Autónoma de Barcelona, Carretera Canyet s/n. 08916-Badalona, Spain

Correspondence: Address correspondence and reprint requests to: Carlos Ferrándiz, MD, PhD; E-mail: cferrandiz.germanstrias{at}gencat.net.

Background: We performed this study to evaluate the clinical effect of microscopic and submicroscopic metastases in sentinel lymph nodes (SLNs) from patients with early-stage melanoma.

Methods: Patients with confirmed cutaneous melanoma (American Joint Committee on Cancer stages I and II) underwent standard lymphoscintigraphy and SLN biopsy. Serial sections were divided between routine histopathology with hematoxylin and eosin plus immunohistochemistry for HMB-45 and molecular analysis by nested reverse transcriptase-polymerase chain reaction (RT-PCR) assay for tyrosinase (using ß-actin as a control).

Results: Of 180 patients analyzed (318 SLNs), 38 (21%) patients had positive SLN(s) by routine hematoxylin and eosin and immunohistochemistry (microscopic disease; group 1), and 142 (79%) had negative histological results. Analysis by RT-PCR detected tyrosinase in at least 1 SLN from 124 (69%) patients. Among patients with histologically negative SLN(s), tyrosinase was detected in 86 (48%) patients (submicroscopic disease; group 2), whereas 40 (22%) patients had negative results by both histology and RT-PCR (group 3). Sixteen (9%) patients had histologically negative SLNs and ambiguous RT-PCR results (group 4). Among 138 patients in the analysis of recurrence (mean follow-up, 45 months), only 18 patients had a recurrence: 11 (31%) of 35 in group 1, 5 (10%) of 51 in group 2, and 2 (5%) of 37 in group 3. No recurrences were seen in group 4. Only group 1 had a significantly shorter disease-free survival and overall survival compared with the other groups.

Conclusions: After a long follow-up period, molecular upstaging by tyrosinase RT-PCR failed to detect a subgroup of patients with an increased probability of recurrence.

Key Words: Melanoma • Molecular staging • Reverse transcriptase-polymer chain reaction • Tyrosinase • Sentinel lymph node

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