Clinical relevance of molecular staging for melanoma - Comparison of RT-PCR and immunohistochemistry staining in sentinel lymph nodes of patients with melanoma

Objective To determine the clinical significance of a molecular assay based on the reverse transcriptase polymerase chain reaction (RT-PCR) for the pr esence of micrometastatic melanoma cells in sentinel lymph nodes (SLNs). Summary Background Data Routine histologic examination of lymph nodes often underestimates the presence of micrometastatic disease. The authors have p reviously shown that an RT-PCR assay designed to detect melanocyte-specific expression of the tyrosinase gene could be used to define a population of patients at higher risk for both recurrence and death compared with routine hematoxylin and eosin (H&E) histology. In this study, the authors used the tyrosinase RT-PCR assay in a patient population examined by a more detaile d histologic analysis, including S-100 immunohistochemistry. Methods Patients underwent lymphatic mapping and SLN biopsy. SLN specimens were bivalved, and half of each specimen was serially sectioned and examine d by routine H&E histology and S-100 immunohistochemistry. The other half o f each specimen was analyzed by a nested RT-PCR assay. Results Hematoxylin and eosin histology detected metastatic disease in 36 ( 16%) of the 233 patients tested. S-100 immunohistochemistry detected microm etastatic disease in another 16 patients, and 114 (63%) of 181 patients wit h histology-negative nodes had positive findings on RT-PCR. There were sign ificant differences between PCR-positive and PCR-negative patient groups in Breslow thickness, Clark level, and the presence of ulceration of the prim ary tumor, factors that have been shown to correlate with recurrence and su rvival. Conclusions These results suggest that RT-PCR can increase the sensitivity of detection of metastatic melanoma cells in SLNs over the current standard methods, including H&E histology and S-100 immunohistochemistry. Further l ong-term follow-up is needed to detect actual differences in recurrence and overall survival.