Receptors for the liver synthesized growth factors IGF-1 and HGF/SF in uveal melanoma: intercorrelation and prognostic implications.
OBJECTIVE
Uveal melanoma disseminates preferentially to the liver. The mechanism for this homing is largely unknown, but growth factors synthesized in the liver may be involved. The present study was undertaken to investigate the possible relationship between cell surface receptors for two such growth factors: the c-Met proto-oncogene, which constitutes the receptor for hepatocyte growth factor/scatter factor (HGF/SF), and the insulin-like growth factor 1 receptor (IGF-1R). Their role as a prognostic factor was also clarified.


METHODS
Paraffin-embedded tumor specimens from 132 patients with primary uveal melanoma were analyzed by using well-established specific antibodies against c-Met and IGF-1R. The intercorrelation of receptor expression and association with melanoma-related survival of patients were determined by univariate and multivariate analyses.


RESULTS
Whereas the expression of both IGF-1R and c-Met was significantly associated with melanoma-specific mortality by univariate analysis (p = 0.004 and p = 0.007, respectively) only IGF-1R showed independent prognostic value by multivariate analysis, p = 0.004. The prognostic value of IGF-1R was stronger than such currently used prognostic parameters as tumor cell type and tumor diameter (p = 0.021 and p = 0.026, respectively). The expression patterns of the two growth factors receptors were weakly intercorrelated.


CONCLUSIONS
In conclusion, the data suggest that the receptors for IGF-1 and HGF/SF may play a role in the spread of uveal melanoma and its affinity to the liver. The strong correlation between IGF-1R expression and melanoma-specific mortality points to the use of IGF-1R as a prognostic tool [Economou MA, All-Ericsson C, Bykov V, Girnita L, Bartolazzi A, Larsson O & Seregard S (2005): Receptors for the liver synthesized growth factors IGF-1 and HGF/SF in uveal melanoma: intercorrelation and prognostic implications.
Economou
Mario A
MA
Cellular and Molecular Tumor Pathology, Department of Oncology and Pathology, Karolinska Hospital, Stockholm, Sweden.
All-Ericsson
Charlotta
C
Bykov
Vladimir
V
Girnita
Leonard
L
Bartolazzi
Armando
A
Larsson
Olle
O
Seregard
Stefan
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007158:Immunologic Techniques; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000378:metabolism*; D013194:Staining and Labeling; D014604:Uveal Neoplasms / Q000378:metabolism* / Q000401:mortality
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met; D017526:Receptor, IGF Type 1