Using the direct-injection model of early uveal melanoma hepatic metastasis to identify TPS as a potentially useful serum biomarker.
OBJECTIVE
To develop a method to screen for serum biomarkers of early hepatic metastasis from uveal melanoma.


METHODS
Cytokeratin 18 (TPS) was identified from gene expression profiles as protein generated by highly invasive uveal melanoma cells. Sera were collected from two groups of 15 SCID mice 2 weeks after injection of either tissue culture medium or MUM2B human metastatic uveal melanoma cells into the mouse liver. Serum TPS levels were assayed in 53 healthy human controls, 64 uveal melanoma patients who were disease free for at least 10 years, and 37 patients with metastatic uveal melanoma.


RESULTS
After 2 weeks, small hepatic nodules (0.1-2.8 mm; mean, 0.80 mm) developed in 11 of 15 mice injected with MUM2B cells. Serum TPS levels in media-injected mice (84.7 U/L) were substantially lower than levels in MUM2B-injected mice (601 mug/L). TPS levels were significantly higher (P < 0.0001) in patients with metastatic uveal melanoma (139.63 +/- 22.20) than in healthy controls (54.23 +/- 0.01) or in patients free of disease (69.29 +/- 9.76). Significant differences were found between TPS levels before and after the development of hepatic metastases (P < 0.01), and serum TPS levels became elevated in four patients at least 6 months before the detection of hepatic metastases by abdominal ultrasonography.


CONCLUSIONS
The direct-injection model of uveal melanoma in the mouse liver may be used to screen for potential serum biomarkers of metastatic uveal melanoma.
Barak
Vivian
V
Immunology Laboratory for Tumor Diagnosis, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Frenkel
Shahar
S
Valyi-Nagy
Klara
K
Leach
Lu
L
Apushkin
Marsha A
MA
Lin
Amy Y
AY
Kalickman
Inna
I
Baumann
Nikola A
NA
Pe'er
Jacob
J
Maniotis
Andrew J
AJ
Folberg
Robert
R
D000818:Animals; D000951:Antigens, Neoplasm / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D006801:Humans; D053538:Keratin-18 / Q000097:blood; D008113:Liver Neoplasms / Q000097:blood* / Q000556:secondary; D008545:Melanoma / Q000097:blood* / Q000556:secondary; D051379:Mice; D016513:Mice, SCID; D010455:Peptides / Q000097:blood*; D014407:Tumor Cells, Cultured; D014604:Uveal Neoplasms / Q000097:blood* / Q000473:pathology
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D053538:Keratin-18; D010455:Peptides; C089984:tissue polypeptide specific antigen