HER2 overexpression correlates with survival after curative resection of pancreatic cancer

Cancer Science - Tập 100 Số 7 - Trang 1243-1247 - 2009
Masahiro Komoto1, Bunzo Nakata1, Ryosuke Amano1, Noriko Yamada1, Masakazu Yashiro1, Masaichi Ohira1, Kenichi Wakasa2, Kosei Hirakawa1
1Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka
2Division of Pathology, Osaka City University Hospital, Osaka, Japan

Tóm tắt

HER2 overexpression has been linked to clinical outcomes in several solid tumors, such as breast cancer. However, the correlation between HER2 overexpression and survival in pancreatic carcinoma remains unclear. The impact of HER2 overexpression on survival in pancreatic ductal cancer was examined. Immunohistochemical staining of 129 pancreatic cancers without hematogenous metastases or peritoneal dissemination treated by macroscopically curative resection were analyzed in association with survival data. To determine HER2 overexpression in this pancreatic cancer series, the polyclonal antibody included in HercepTest, which is used worldwide for clinical examination of HER2 overexpression in breast cancer, was used. Immunoreactivity was classified according to the scale presented in the HercepTest Scoring Guidelines. Twenty‐two cases (17.1%) had a score of 0, 28 cases (21.7%) had of a score of 1+, 41 cases (31.8%) had a score of 2+, and 38 cases (29.4%) had a score of 3+. Therefore, HER2 overexpression (score 2+ or 3+) was observed in 79 cases (61.2%). Patients with HER2 overexpression tumors had significantly shorter survival times than those with HER2 normal expression (score 0 or 1+) tumors (median survival time, 14.7 vs 20.7 months, respectively; P = 0.0078 on the log‐rank test). On multivariate survival analysis, HER2 overexpression remained an independent prognostic factor (hazard ratio, 1.806; P = 0.0258). A significant percentage of pancreatic cancers were demonstrated to have HER2 overexpression, and overexpression of this tyrosine kinase receptor proved to be an independent factor for a worse prognosis. These results should encourage further investigation of treatments using new molecular targeting agents against HER2 protein to improve the survival of pancreatic cancer patients. (Cancer Sci 2009; 100: 1243–1247)

Từ khóa


Tài liệu tham khảo

10.1126/science.2999974

10.1056/NEJMra0707704

10.1023/A:1006384521198

10.1126/science.3798106

10.1126/science.2470152

10.1038/ng1215

10.1038/modpathol.3880505

10.1097/00129039-200309000-00003

Kern JA, 1990, p185neu expression in human lung adenocarcinomas predicts shortened survival, Cancer Res, 50, 5184

10.1007/BF01629433

10.1007/s10620-005-9057-1

Lei S, 1995, Overexpression of HER2/neu oncogene in pancreatic cancer correlates with shortened survival, Int J Pancreatol, 17, 15, 10.1007/BF02788354

10.1016/0046-8177(93)90194-L

Koka V, 2002, Role of immunohistochemical identification of Her‐2/neu and detection of variability in overexpression in pancreatic carcinoma, Anticancer Res, 22, 1593

Sobin LH, 2002, TNM. Classification of Malignant Tumors, 93

10.1016/S0046-8177(96)90364-0

10.1097/01.pas.0000160979.85457.73

10.3816/CBC.2005.n.026

Petit AM, 1997, Neutralizing antibodies against epidermal growth factor and ErbB‐2/neu receptor tyrosine kinases down‐regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors, Am J Pathol, 151, 1523

10.1200/JCO.2004.05.142

10.1200/JCO.2002.20.3.719

10.1158/1078-0432.CCR-06-0544

10.1081/CNV-200032974

Rusnak DW, 2001, The effects of the novel, reversible epidermal growth factor receptor/ErbB‐2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor‐derived cell lines in vitro and in vivo, Mol Cancer Ther, 1, 85

10.1056/NEJMoa064320