Serum markers to detect metastatic uveal melanoma.
BACKGROUND
Osteopontin (OPN) is overexpressed in metastatic uveal melanoma (UM). S-100beta and melanoma-inhibitory activity (MIA) serum levels are elevated in metastatic cutaneous melanoma. The ability of OPN, S-100beta and MIA serum levels to be used as non-invasive markers for detecting metastatic UM was tested.


METHODS
OPN, S-100beta and MIA levels were measured by ELISA assays in 18 patients with metastatic UM and in 38 patients who were disease-free (DF) for at least 10 years after treatment of the primary tumor. Paired serum samples from 8 patients before and after development of metastasis were analyzed. Forty-four healthy controls (C) were compared to the other two groups.


RESULTS
Serum OPN, MIA, and S-100beta levels were significantly higher in patients with metastatic UM as compared to patients who were DF for at least 10 years after treatment (p = 0.0001) or with age-matched controls. Serum OPN, MIA and S-100beta levels were significantly higher (p < 0.005) after metastasis formation than before the clinical detection of metastasis in the 8 patients. Receiver operator characteristic analysis was performed for metastatic patients vs. DF and vs. C, and the area under the curve was calculated for each marker and for the combination of the 3 markers, which was 91%.


CONCLUSIONS
Elevated serum OPN, MIA and S-100beta levels correlate with metastatic UM to the liver. When used in combination, these markers provide a highly sensitive and specific method to detect hepatic metastases and therefore provide for earlier therapeutic intervention that can prolong survival.
Barak
Vivian
V
Immunology Laboratory for Tumor Diagnosis, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. hamon@bezeqint.net
Frenkel
Shachar
S
Kalickman
Inna
I
Maniotis
Andrew J
AJ
Folberg
Robert
R
Pe'er
Jacob
J
D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000175:diagnosis*; D009363:Neoplasm Proteins / Q000097:blood; D009414:Nerve Growth Factors / Q000097:blood; D053495:Osteopontin / Q000097:blood; D012372:ROC Curve; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D012680:Sensitivity and Specificity; D014604:Uveal Neoplasms / Q000097:blood* / Q000175:diagnosis*
D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; C090059:MIA protein, human; D009363:Neoplasm Proteins; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D053495:Osteopontin