S100-Beta, melanoma-inhibiting activity, and lactate dehydrogenase discriminate progressive from nonprogressive American Joint Committee on Cancer stage IV melanoma.
OBJECTIVE
Monitoring advanced malignant melanoma, serum levels of S100-beta (S100beta) and melanoma-inhibiting activity (MIA) were assessed for the ability to discriminate progressive from nonprogressive disease. S100beta and MIA were supposed to be superior to conventional variables, such as lactate dehydrogenase (LDH) level.


METHODS
Seventy-one patients with stage IV malignant melanoma according to the criteria of the American Joint Committee on Cancer (AJCC) were included in the study. Results of restaging examinations were used as an independent reference standard for diagnosing progressive disease, and S100beta, MIA, LDH level, and erythrocyte sedimentation rate (ESR) were determined in venous blood just before restaging. Sensitivities and specificities of the parameters were calculated by logistic regression analysis. Discrimination ability was assessed by Somers' D(xy) rank correlation and the area under the receiver-operating characteristic curve (ROC-AUC).


RESULTS
All tested serum parameters were significantly elevated in patients with progressive disease. The highest sensitivities according to the established thresholds were found for S100beta and MIA (91% and 88%, respectively). LDH had the highest specificity (92%). ESR was dropped from the analysis because of low specificity. In calculating Somers' D(xy) and ROC-AUC values, S100beta, MIA, and LDH showed high discrimination ability. By multiple logistic regression, LDH was identified to be the only statistically significant marker for progressive disease. S100beta and MIA did not provide additional significant information because of their high correlation with LDH with respect to clinical outcome.


CONCLUSIONS
Elevated serum levels of S100beta, MIA, and LDH indicate current disease progression in AJCC stage IV melanoma. LDH was the most relevant overall parameter.
Deichmann
M
M
Department of Dermatology, University of Heidelberg, and Central Unit of Biostatistics R0700, German Cancer Research Center, Heidelberg, Germany.
Benner
A
A
Bock
M
M
Jäckel
A
A
Uhl
K
K
Waldmann
V
V
Näher
H
H
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood; D001799:Blood Sedimentation; D018450:Disease Progression; D016326:Extracellular Matrix Proteins; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008545:Melanoma / Q000097:blood / Q000175:diagnosis* / Q000201:enzymology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D009367:Neoplasm Staging / Q000379:methods*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012016:Reference Values; D009418:S100 Proteins / Q000097:blood*; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000201:enzymology
D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; C090059:MIA protein, human; D009363:Neoplasm Proteins; D009418:S100 Proteins; C110294:S100A1 protein; D007770:L-Lactate Dehydrogenase