Detection of occult melanoma cells in paraffin-embedded histologically negative sentinel lymph nodes using a reverse transcriptase polymerase chain reaction assay

J Clin Oncol. 2001 Mar 1;19(5):1437-43. doi: 10.1200/JCO.2001.19.5.1437.

Abstract

Purpose: Detection of occult metastasis before the development of clinical disease could allow more accurate staging, appropriate follow-up procedures, and adjuvant therapies in patients with malignant melanoma (MM). The sentinel lymph node (SLN) has been proposed as a reliable predictor of metastatic disease in the lymphatic basin draining the primary melanoma. In this study, we screened both paraffin-embedded SLNs and peripheral-blood (PB) samples from MM patients at various stage of disease using a multimarker reverse transcriptase polymerase chain reaction (RT-PCR) assay. The prognostic significance of the presence of PCR-positive markers was also evaluated.

Patients and methods: Total RNA was obtained from paraffin-embedded SLN sections and PB samples of 75 MM patients. RT-PCR was performed using tyrosinase and MelanA/MART1 as melanoma-associated markers. Radiolabeled PCR products were analyzed on denaturing polyacrylamide gels.

Results: Good sensitivity of the RT-PCR assay on archival tissues was demonstrated after comparison of RT-PCR results on frozen and paraffin-embedded SLNs from 16 MM patients. Significant correlation between the disease stage and marker expression in both PB and SLN samples was observed; the highest value was for patients who were positive for both markers in SLN (P =.006). Progression of disease was significantly associated with the total number of PCR-positive markers in both PB (P =.034) and SLN (P =.001) samples.

Conclusion: Although sensitivity is lowered by the use of paraffin-embedded specimens, our data indicate that RT-PCR analysis of serial sections from archival SLNs may be helpful in improving detection of occult micrometastases, thus improving staging of patients with melanoma.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis
  • DNA, Neoplasm / analysis
  • False Negative Reactions
  • Humans
  • Lymphatic Metastasis / diagnosis
  • Melanoma / diagnosis*
  • Melanoma / pathology
  • Paraffin Embedding
  • Prognosis
  • Reverse Transcriptase Polymerase Chain Reaction / standards*
  • Sensitivity and Specificity
  • Sentinel Lymph Node Biopsy*
  • Skin Neoplasms / diagnosis*
  • Skin Neoplasms / pathology
  • Specimen Handling

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm