Diagnostic value and prognostic significance of protein S-100beta, melanoma-inhibitory activity, and tyrosinase/MART-1 reverse transcription-polymerase chain reaction in the follow-up of high-risk melanoma patients.
BACKGROUND
Cutaneous melanoma is the most aggressive form of skin carcinoma in humans, frequently with a rapid progression of disease. To detect early developing metastasis, laboratory tests to determine levels of lactate dehydrogenase (LDH) and alkaline phosphatase (AP) form part of the regular follow-up, but often cannot discover recurrent disease at a sufficiently early stage.


METHODS
To evaluate the diagnostic accuracy of protein S-100beta (S-100beta), melanoma-inhibitory activity (MIA), LDH, AP, and tyrosinase/MART-1 reverse transcription-polymerase chain reaction (RT-PCR), the authors included 296 consecutive AJCC Stage II or III clinically disease-free melanoma patients. Follow-up examinations were performed every 3 months and blood samples were drawn to determine the levels of these tumor markers.


RESULTS
Metastasis occurred in 41 of the 296 patients during a median follow-up period of 19 months (range, 1-33 months). The sensitivity to detect new metastases was 29% for protein S-100beta, 22% for MIA, 2% for LDH, 17% for AP, and 24% for RT-PCR. The diagnostic accuracy was best for MIA (86%) and S-100beta (84%), whereas AP (79%), LDH (77%), and RT-PCR (72%) demonstrated lower values. Elevated values of S-100beta and MIA during follow-up examinations were associated with decreased survival rates in the further course of the disease, but pathologic findings of the other tumor markers showed no prognostic impact.


CONCLUSIONS
To the authors' knowledge, the current study is the first comparison of the diagnostic accuracy of currently available tumor markers in the follow-up of high-risk melanoma patients. Protein S-100beta and MIA demonstrated a higher sensitivity, specificity, and diagnostic accuracy in the diagnosis of newly occurring metastasis compared with to the tumor markers AP, LDH, and RT-PCR diagnostics. Therefore, the tumor markers S-100beta and MIA may be useful in the follow-up of disease-free Stage II and III melanoma patients.
Garbe
Claus
C
Department of Dermatology, Skin Cancer Program, Eberhard-Karls-University of Tuebingen, Tuebingen, Germany. claus.garbe@med.uni-tuebingen.de
Leiter
Ulrike
U
Ellwanger
Ulf
U
Blaheta
Hans-Juergen
HJ
Meier
Friedegund
F
Rassner
Gernot
G
Schittek
Birgit
B
D000328:Adult; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000032:analysis*; D016326:Extracellular Matrix Proteins; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000175:diagnosis*; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis; D009363:Neoplasm Proteins / Q000032:analysis*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D009414:Nerve Growth Factors; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012306:Risk; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000032:analysis*; D012878:Skin Neoplasms / Q000175:diagnosis*; D013997:Time Factors
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; D058965:MART-1 Antigen; C090059:MIA protein, human; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins