Serum protein s-100 predicts clinical outcome in patients with melanoma treated with adjuvant interferon--comparison with tyrosinase rt-PCR.
OBJECTIVE
To study the clinical value of the determination of serum S-100 protein as a single tumor marker or in combination with tyrosinase RT-PCR in patients with melanoma receiving adjuvant interferon.


METHODS
Patients were tested for serum S-100 protein luminoimmunometric assay and for blood tyrosinase mRNA (RT-PCR), before starting interferon and every 2-3 months thereafter.


RESULTS
One hundred and six patients (stage IIA, 27; IIB, 19; III, 49; and IV, 11) were included in the study. Median follow-up was 51 months (range 2-76). In the univariate analysis, under treatment S-100 > or =0.15 microg/l and a positive RT-PCR correlated with a lower disease-free survival and overall survival (OS). In the multivariate analysis, clinical stage, under therapy positive RT-PCR and S-100 levels > or =0.15 mug/ml, were independent prognostic factors for OS. The hazard ratio for OS was 3.9 (95% CI, 1.67-9.15; p = 0.004) and 2.2 (95% CI, 1.05-4.6; p = 0.016) for S-100 > or =0.15 microg/l and positive RT-PCR, respectively. When both techniques where combined, a positive RT-PCR indicated a poorer clinical outcome only in patients with S-100 <0.15 microg/l.


CONCLUSIONS
S-100 > or =0.15 microg/l and a positive RT-PCR during adjuvant interferon therapy indicate a high risk of death in resected melanoma patients. S-100 determination has a higher positive predictive value than RT-PCR, while tyrosinase RT-PCR adds prognostic information in patients with S-100 <0.15 microg/l.
Domingo-Domènech
J
J
Medical Oncology Department, Biochemistry Department, Hospital Clínic, IDIBAPS, Melanoma Group, Barcelona, Spain. 33884jdd@COMB.es
Molina
R
R
Castel
T
T
Montagut
C
C
Puig
S
S
Conill
C
C
Martí
R
R
Vera
M
M
Auge
J M
JM
Malvehy
J
J
Grau
J J
JJ
Gascon
P
P
Mellado
B
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000188:drug therapy; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009418:S100 Proteins / Q000097:blood*; D012878:Skin Neoplasms / Q000097:blood / Q000188:drug therapy
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D009418:S100 Proteins; D014442:Monophenol Monooxygenase