Serial follow-up and the prognostic significance of reverse transcriptase-polymerase chain reaction--staged sentinel lymph nodes from melanoma patients.
OBJECTIVE
Reverse transcriptase-polymerase chain reaction (RT-PCR) may provide an extremely sensitive method for detection of occult nodal disease. We evaluated the role of a single-marker RT-PCR assay for tyrosinase mRNA in the detection of melanoma sentinel lymph node (SLN) metastases and correlated the results with long-term clinical outcome.


METHODS
One hundred twelve patients who underwent SLN biopsy for melanoma were prospectively analyzed. SLNs were bivalved, with half of each specimen evaluated by histologic methods and the other half evaluated by nested RT-PCR for tyrosinase.


RESULTS
Fifteen patients (13%) had histologically positive SLNs, all of whom were also positive by RT-PCR (HISTO+/PCR+). Thirty-nine patients (35%) had SLNs that were negative by both histology and RT-PCR (HISTO-/PCR-). Fifty-eight patients (52%) were histologically negative but upstaged with a positive RT-PCR result (HISTO-/PCR+). Initially, at a median follow-up of 42 months, recurrence rates among the three cohorts were statistically different (HISTO+/PCR+, 53%; HISTO-/PCR+, 14%; and HISTO-/PCR-, 0%). However, at a longer median follow-up (67 months), recurrence rates for the HISTO-/PCR+ (24%) and HISTO-/PCR- (15%) groups were no longer statistically different (P =.25). The median time to relapse between the HISTO-/PCR+ and HISTO-/PCR- groups differed by 10 months (31 v 41 months, respectively).


CONCLUSIONS
With extended follow-up of patients with histologically negative SLNs, detection of submicroscopic disease by tyrosinase RT-PCR does not define a subgroup that is at higher recurrence risk when compared with patients with RT-PCR-negative SLNs. Future studies evaluating molecular staging will require approximately 5 years of median follow-up to accurately define outcome for patients with occult melanoma metastases.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. udai_kammula@nih.gov
Udai S
US
Kammula
Ronald
R
Ghossein
Satyajit
S
Bhattacharya
Daniel G
DG
Coit
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000473:pathology*; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000235:genetics*; D016612:Paraffin Embedding; D011237:Predictive Value of Tests; D011379:Prognosis; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology*; D015996:Survival Rate
D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm; D014442:Monophenol Monooxygenase