Prognostic significance of occult metastases detected by sentinel lymphadenectomy and reverse transcriptase-polymerase chain reaction in early-stage melanoma patients

Purpose: Detection of micrometastases in the regional tumor-draining lymph nodes is critical for accurate staging and prognosis in melanoma patients. We hypothesized that a multiple-mRNA marker (MM) reverse transcriptase-poly merase chain reaction (RT-PCR) assay would improve the detection of occult metastases in the sentinel node (SN), compared with hematoxylin and eosin ( H&E) staining and immunohistochemistry (IHC), and that MM expression is pre dictive of disease relapse, Patients and Methods: Seventy-two consecutive patients with clinical early- stage melanoma underwent sentinel lymphadenectomy (SLND). Their SNs were se rially sectioned and assessed for MAGE-3, MART-1, and tyrosinase mRNA expre ssion by RT-PCR, in parallel with H&E staining and IHC, for melanoma metast ases, MM expression in the SNs was correlated with H&E and IHC assay result s, standard prognostic factors, and disease-free survival. Results: In 17 patients with H&E- and/or IHC-positive SNs, 16 (94%) express ed two or more mRNA markers. Twenty (36%) of 55 patients with histopatholog ically negative SNs expressed two or more mRNA markers. By multivariate ana lysis, patients at increased risk of metastases to the SN had thicker lesio ns (P = .03), were 60 years of age or younger (P < .05), and/or were MM-pos itive (P < .001), patients with histopathologically melanoma-free SNs who w ere MM-positive, compared with those who were positive for one or fewer mRN A markers, were at increased risk of recurrence (P = .02). Patients who wer e MM-positive with histopathologically proven metastases in the SN were at greatest risk of disease relapse (P = .01), Conclusion: H&E staining and IHC underestimate the true incidence of melano ma metastases, MM expression in the SN more accurately reflects melanoma mi crometastases and is also a more powerful predictor of disease relapse than are H&E staining and IHC alone. (C) 1999 by American Society of Clinical O ncology.