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

Cancer. 2003 Apr 1;97(7):1737-45. doi: 10.1002/cncr.11250.


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.

MeSH terms

  • Adult
  • Antigens, Neoplasm
  • Biomarkers, Tumor / analysis*
  • Extracellular Matrix Proteins
  • Female
  • Follow-Up Studies
  • Humans
  • MART-1 Antigen
  • Male
  • Melanoma / diagnosis*
  • Middle Aged
  • Neoplasm Metastasis / diagnosis
  • Neoplasm Proteins / analysis*
  • Neoplasm Recurrence, Local / diagnosis
  • Nerve Growth Factors
  • Prognosis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins / analysis*
  • Skin Neoplasms / diagnosis*
  • Time Factors


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Extracellular Matrix Proteins
  • MART-1 Antigen
  • MIA protein, human
  • MLANA protein, human
  • Neoplasm Proteins
  • Nerve Growth Factors
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins