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Correlation With Clinical Outcome

Steven C. Shivers, PhD; Xiangning Wang, MD; Weiguo Li, MD; Emmanuella Joseph, MD; Jane Messina, MD; L. Frank Glass, MD; Ronald DeConti, MD; C. Wayne Cruse, MD; Claudia Berman, MD; Neil A. Fenske, MD; Gary H. Lyman, MD, MPH; Douglas S. Reintgen, MD

JAMA. 1998;280:1410-1415.

Context.— For most solid tumors, the metastatic status of regional lymph nodes is the strongest predictor of relapse and survival. However, routine pathological examination of lymph nodes may underestimate the number of patients with melanoma who have nodal metastases.

Objective.— To determine the clinical significance of a highly sensitive molecular assay for occult nodal metastases for the staging of patients with melanoma.

Design.— A prospective cohort study of consecutive patients in which lymphatic mapping and sentinel lymph node (SLN) biopsy were performed on 114 melanoma patients with clinical stage I and stage II disease. The SLNs were bivalved, and half of each specimen was submitted for routine pathological examination. The other half was submitted for molecular detection of submicroscopic metastases using a reverse transcriptase–polymerase chain reaction (RT-PCR) assay for tyrosinase messenger RNA as a marker for the presence of melanoma cells. Patient follow-up averaged 28 months.

Setting.— A major university-based melanoma referral center at a National Cancer Institute–designated cancer center.

Patients.— A total of 114 patients with newly diagnosed cutaneous malignant melanoma who were at risk for regional nodal metastases.

Main Outcome Measure.— Melanoma recurrence and overall survival.

Results.— Twenty-three patients (20%) had pathologically positive SLNs, and all of these patients were also RT-PCR positive. Of the 91 pathologically negative patients, 44 were RT-PCR negative and 47 were RT-PCR positive. There was a recurrence rate among 14 (61%) of the 23 patients who were both pathologically and RT-PCR positive and a recurrence rate among 1 (2%) of 44 patients who were both pathologically and RT-PCR negative. For patients who were upstaged by the molecular assay (pathologically negative, RT-PCR positive), there was a recurrence rate among 6 (13%) of 47 patients. The differences in recurrence rates and overall survival between the pathologically negative, RT-PCR–negative and pathologically negative, RT-PCR–positive patient groups were statistically significant (P=.02 for disease-free survival and for overall survival). In both univariate and multivariate regression analyses, the histological and RT-PCR status of the SLNs were the best predictors of disease-free survival.

Conclusions.— The use of an RT-PCR assay for detection of submicroscopic melanoma metastases in SLNs improved the prediction of melanoma recurrence and overall survival over routine pathological examination.

From the Cutaneous Oncology Program, H. Lee Moffitt Cancer Center and Research Institute (Drs Shivers, Wang, Li, Joseph, Messina, Glass, DeConti, Cruse, Berman, Fenske, and Reintgen), and the Departments of Surgery (Drs Shivers, Wang, Li, Joseph, Cruse, and Reintgen), Pathology and Laboratory Medicine (Drs Messina and Glass), Internal Medicine (Drs DeConti, Fenske, and Lyman), and Radiology (Dr Berman), University of South Florida, Tampa.

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