Abstract 1097: Immunohistochemical expression of growth factor receptors in different stages of human cutaneous melanoma

Abstract

Abstract Background: Melanoma is an aggressive and chemoresistant tumor.High risk melanoma is minimally susceptible to current treatment strategies.These treatment strategies have not yielded much appreciable survival benefits. It is now clearly evident that cell-surface receptors play a pivotal role in transmitting extracellular signals to intracellular effectors. Trophic factors exert profound influence on the tumor micro-environment through auto or paracrine signaling mechanisms in the course of coordinated activation of their cognate receptors.This in turn orchestrates tumor growth, survival and invasion. Melanoma cells utilize a cascade of multiple trophic factors which modulate tumor progression through autocrine growth mechanisms by activating specific receptor tyrosine kinases (RTKs). Melanoma progression is preceded with certain types of cells oscillating in response to changing micro-environment signals. Therefore, growth factor receptor activation in melanoma cells may have important implications in tumor progression and tumor cell homing to metastatic sites.The aim of present investigation was to assess synergistic expression of EGF-R, FGF-R,VEGF-R, PDGF-R, IGF-1R,TGFβ-RII at various stages of cutaneous melanoma by Immunohisto-chemistry in order to identify factors that might be applied to early diagnosis, prognosis or for emerging targeted therapies. Methods: FFPE tissues were selected from patients with primary melanoma (n=39), metastatic melanoma (n=19) and 11 patients with benign nevi. Five micron thick sections of FFPE tissues from each case were subjected individually for Immunohistochemical staining using monoclonal / polyclonal antibodies to EGFR, phosphoEGFR, FGF-R, VEGF-R3, PDGF-Rβ, IGF1R, TGFβ-RII. Immunoexpression patterns of various growth factor receptors were evaluated with a semi-quantitative scoring system for the intensity of staining on tumor cells.Fisher's exact test was utilized to determine significant variance in the study group. Results: Tissues from patients with metastatic melanoma revealed significant overexpression of IGF1-R, TGF-β RII when compared with primary melanoma (p<.0.008, p<0.0214) while overexpression of phospho-EGF-R in metastatic melanoma was also found to be significant (p<0.033) as compared to nevi. Further, FGF-R1 was also found to be significantly overexpressed in primary melanoma in comparison with nevi (p<0.0001).No significant differences in the overexpression of EGFR, VEGF-R3, PDGF-Rβ were observed in this study group. Conclusions: The study revealed overexpression of TGFβ-RII, IGF1R, FGFR1 and phosho-EGF-R which are suggestive of the markers of receptor tyrosine kinase dependent progression of metastatic lesions through activation of multiple signaling pathways. Multi-targeted therapeutics will be a better paradigm for effective clinical management of high risk cutaneous melanoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1097. doi:10.1158/1538-7445.AM2011-1097