Overexpression of Epidermal Growth Factor Receptor Restricted to Macrophages in Uveal Melanoma

Abstract

To determine whether expression of the epidermal growth factor receptor (EGFR) is of prognostic value in uveal melanoma. Methods: Thirty consecutive patients treated for primary posterior uveal melanoma by enucleation or local resection were studied. Tumors were examined for EGFR and CD68 expression by immunohistochemistry on formalin-fixed, paraffin-embedded sections. Extracted DNA from paired frozen tumor and blood samples was examined for loss of heterozygosity on chromosome 3 using polymerase chain reaction-based microsatellite analysis. Immunoreactivity for EGFR was correlated with clinicopathological, chromosome 3, and follow-up data. Results: Immunoreactivity for EGFR was observed in 7 (23%) of 30 uveal melanomas, but was restricted to solitary or small groups of cells with macrophage-like morphology. Immunoreactive cells were confirmed as macrophages using an antibody to the macrophage marker CD68. Chromosome 3 loss, epithelioid cells, and microvascular loops were detected in 17 (57%), 22 (73%) and 19 (63%) of the 30 tumors, respectively. Metastatic disease was detected in 5 patients (17%). No correlation was found between any of these variables and EGFR positivity. Conclusions: The absence of EGFR immunoreactivity in tumor cells does not support the use of EGFR expression as a prognostic indicator in patients with uveal melanoma. Future EGFR studies in uveal melanoma should be interpreted with caution in view of our findings that tumor-associated macrophages can express this receptor.

Expression and amplification of therapeutic target genes in retinoblastoma

“…EGFR overexpression has previously been reported to occur in various tumor types, especially in brain tumors and squamous cell carcinomas [1,6,18,34]. Our data show that retinoblastoma belongs to the group of tumor entities with a marked frequency of EGFR overexpression.…”

Correlation of clinicopathological parameters with HGF, c-Met, EGFR, and IGF-1R expression in uveal melanoma

“…In a study on frozen sections of 21 primary uveal melanomas, EGFR expression was detected in 6 tumors, and this expression was significantly correlated with metastatic disease [16]. However, Scholes et al [17] did not support the use of EGFR as a prognostic indicator, because the immunoreactivity in this study was restricted to a small EGF, epidermal growth factor; HGF, hepatocyte growth factor; IGF-1, insulin-like growth factor 1. Changes in serum epidermal growth factor (EGF) (a), hepatocyte growth factor (HGF) (b), and insulin-like growth factor-1 (IGF-1) (c) levels after enucleation.…”

Expression of Epidermal Growth Factor Receptor, Ezrin, Hepatocyte Growth Factor, and c-Met in Uveal Melanoma: An Immunohistochemical Study

“…However, a later study by Scholes et al 26 did not support the use of EGFR expression as a prognostic indicator in patients with uveal melanoma due to the macrophage-restricted expression of EGFR in uveal melanoma paraffin sections. In our study, in addition to the tumor cells that expressed EGFR, we did observe that macrophage-like cells stained positive for EGFR, confirmed by CD65 staining for macrophages.…”