Molecular staging in stage II and III melanoma patients and its effect on long-term survival.
OBJECTIVE
To assess the prognostic value of serial reverse transcriptase polymerase chain reaction (RT-PCR) -based measurements of tyrosinase mRNA in peripheral blood of stage II and III melanoma patients.


METHODS
During routine follow-up of American Joint Committee on Cancer stage II and III melanoma patients, serial testing for tyrosinase transcripts in peripheral blood was performed by RT-PCR. The PCR results were compared with the clinical data collected during the follow-up.


RESULTS
Over a period of 3 years, 111 patients (78 stage II and 33 stage III patients) were enrolled, and tyrosinase determinations were carried out. The 6-year disease-specific survival probability was 97% for patients always showing negative RT-PCR results and 67% for patients who tested positive at least once. In a Cox proportional hazards model, the prognostic value of sex, age, site of primary tumor, histologic subtype, stage, Breslow's tumor thickness, Clark level, and the time-dependent variable PCR result was assessed. Patients with a positive RT-PCR test had a distinctly higher risk of dying from melanoma, with a hazard ratio of 12.6 (95% CI, 3.4 to 46.3; P < .001).


CONCLUSIONS
Our study shows a strong association between PCR and disease-specific survival time. Detection of tyrosinase mRNA in peripheral blood may be of similar importance for the clinical course of melanoma as the detection of micrometastatic disease in the sentinel lymph node. Whether a combination of these two factors leads to a better definition of the prognosis of melanoma patients is under investigation in current studies.
Voit
Christiane
C
Department of Dermatology of the Charité, Humboldt University, Schumannstr 20/21, 10117 Berlin, Germany. christiane.voit@t-online.de
Kron
Martina
M
Rademaker
Juergen
J
Schwürzer-Voit
Markus
M
Sterry
Wolfram
W
Weber
Lutz
L
Ozdemir
Cueneyt
C
Proebstle
Thomas
T
Keilholz
Ulrich
U
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000097:blood*; D016017:Odds Ratio; D011379:Prognosis; D016016:Proportional Hazards Models; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm; D014442:Monophenol Monooxygenase