Overexpression of HER-2 in thick melanoma

Abstract

In this study we evaluated the overexpression status of HER-2 and its prognostic significance on survival in patients with thick cutaneous malignant melanoma. The immuno-alkaline phosphatase antigen detection technique was applied to archival diagnostic material from 51 patients with primary lesions measuring >or= 10 mm in Breslow thickness. Eleven additional patients with primary lesions measuring <or= 1 mm were also studied. HER-2 overexpression was evaluated using conventional light microscopy and an automated cellular imaging system (Chromavision Medical System). Fifteen (29.4%) out of 51 patients with thick lesions showed HER-2 overexpression. In contrast, no overexpression was seen in any of the thin lesions. Overexpression of HER-2 in this group of patients was of no prognostic significance for freedom from recurrence or survival when studied using univariate and multivariate analyses. Whilst the incidence of HER-2 overexpression in patients with thick cutaneous primary melanoma is similar to that reported in breast cancer, it was of no prognostic significance for survival in this study. However, further evaluation in larger numbers of patients with the full spectrum of Breslow thickness is clearly indicated.

Quantitative Analysis of Surface Plasma Membrane Proteins of Primary and Metastatic Melanoma Cells

“…74 However, conflicting results have been published regarding the expression pattern of erbB-2 in primary and metastatic melanoma. [75][76][77][78] Our proteomic data supported the down-regulation of this receptor in WM-266-4 cells. Other molecules, such as melanoma-associated antigen p97, scavenger receptor and several solute carrier family proteins, also displayed different expression between these two cell lines.…”

T cell recognition of HLA‐A2 restricted tumor antigens is impaired by the oncogene HER2

“…Although the relevance of HER2 in melanoma remains controversial,3, 22 expression of HER2 in melanoma tumor tissue and cell lines has been demonstrated 3, 36, 37. Regardless of its biological and/or clinical significance, the EST049 melanoma cell line can be regarded as a model to study the negative effect of HER2 on MHC class I antigen presentation.…”

“…HER2 is a 185‐kDa glycoprotein member of the epidermal growth factor receptor family of tyrosine kinases and considered one of the most attractive targets for immunotherapeutic interventions 1. This oncogene is selectively over‐expressed in a broad variety of human tumors including 25–40% of breast, ovarian, gastric, renal, esophageal and colorectal carcinomas and a small proportion of human melanomas2–6 and as a cell surface molecule it is accessible both to antibody‐ and T cell‐based approaches. Moreover, HER2 can be regarded as an indispensable tumor antigen, since tumors over‐expressing HER2 are dependent on this oncogene for their survival and silencing consequently leads to growth arrest and/or apoptosis induction 7…”

Biomarkers: The Useful and the Not So Useful—An Assessment of Molecular Prognostic Markers for Cutaneous Melanoma

“…Cross-sectional data were available on 298 proteins. Thirty-one selected proteins, including γ-catenin/plakoglobulin (Silye et al , 1998; Sanders et al , 1999; Zhang and Hersey, 1999; Krengel et al , 2004; Kreizenbeck et al , 2008), Her2/neu (Persons et al , 2000; Fink-Puches et al , 2001; Eliopoulos et al , 2002; Potti et al , 2003a, 2004; Kluger et al , 2004), estrogen receptor-α (Cohen et al , 1990; Schmidt et al , 2006), matrix metalloproteinase-26, and matrix metalloproteinase-28 (Kuivanen et al , 2005), were found not to be expressed in melanoma cells and 18 proteins such as endothelin-3 (Tang et al , 2008), focal adhesion kinase (Hess et al , 2005), matrix metalloproteinase-1 (Nikkola et al , 2001, 2002), and telomerase (Batinac et al , 2007; Zygouris et al , 2007) were evaluated by IHC but cross-sectional data were not reported in their corresponding manuscripts. Among the included proteins, 274 were evaluated in progression studies but a much smaller subset, 148, had their expression levels correlated with Breslow thickness.…”