HER-family gene amplification and expression in resected pancreatic cancer

Abstract

Aims: Despite surgical resection, pancreatic cancer carries a poor prognosis. In search for new molecular therapeutic targets, we investigated the expression of the HER-family and gene amplification of HER-2 in pancreatic adenocarcinomas of different stages.Methods: Tissue of 45 resected patients was analysed for all HER-family 1-4 expression by immunohistochemistry and HER-2 gene amplification was assessed by multiplex ligation-dependent probe amplification and chromogenic in situ hybridization. The type of surgery, location, stage and grade of the tumour, as well as involvement of the resection margins were correlated with HERexpressions and univariate and multivariate survival analysis performed.

HER3 Overexpression as an Independent Indicator of Poor Prognosis for Patients with Curatively Resected Pancreatic Cancer

“…These observations are consistent with the findings of Friess et al [7]and Vaidya et al [8]. However, Kawesha et al [9] and Velde et al [10] found that HER3 overexpression is not a prognostic indicator for pancreatic cancer. The cause of these conflicting results is unclear, but the discrepancy may be due to differences in the methods of immunohistochemical evaluation used by different investigators.…”

“…The cause of these conflicting results is unclear, but the discrepancy may be due to differences in the methods of immunohistochemical evaluation used by different investigators. Specifically, Friess et al [7 ]defined HER3-positive staining as strong membranous and/or cytoplasmic staining in at least 10% of cancer cells, Vaidya et al [8 ]classified tumors as positive if they had focal or diffuse staining with a score of at least 2+ using a 4-point (0 to 3+) scoring scale, Kawesha et al [9 ]defined tumors as positive if there was unequivocal cytoplasmic staining in more than 5% of cancer cells, and Velde et al [10 ]also only examined cytoplasmic staining and used the same criteria as Vaidya et al [8]. We used the same semiquantitative evaluation method and definition of HER3-positive staining as Vaidya et al [8]and Velde et al [10].…”

“…HER3 is expressed in various organs including the gastrointestinal, reproductive, respiratory, urinary, endocrine and nervous systems and the skin. It has major physiological roles of cell proliferation or differentiation as a member of the epidermal growth factor receptor family [14] and has been shown to harbor the pathogenesis for several carcinomas such as breast, gastric, colorectal, ovarian and pancreatic cancer [8,9,10,11,15,16,17,18,19]. …”

“…Kawesha et al [9 ]investigated data from 157 patients with resected pancreatic cancer and found no relation between HER3 overexpression in cancer cells and survival. Velde et al [10,]using univariate and multivariate analysis in their group of 32 patients with resectable pancreatic cancers, also found no significant association between HER3 overexpression and survival. The recent development of therapies that target HER3 [11,12,13] motivated us to investigate the relationship between HER3 overexpression and survival in our patients with curatively resected pancreatic cancer tumors with good follow-up.…”

Expression Patterns of Growth and Survival Genes with Prognostic Implications in Advanced Pancreatic Cancer

“…This could easily be attributed to the small size of the patient population, although two significant factors should be considered. The first is that these biomarkers had almost exclusively been previously studied by immunohistochemistry (1,(11)(12)(13)(22)(23)(24), and not mRNA expression. The second is that most of the factors had never been studied in patients treated with EGFR inhibitors (1,(11)(12)(13).…”