The online version of this article (doi:10.1186/1477-7819-10-274) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
FZ carried out the experiment and data acquisition, and drafted the manuscript. NL helped with the experiment and data acquisition. WJ helped with the literature research. ZH and LX participated in collecting the samples. QW helped with writing, discussion of and editing the manuscript. LW designed the study, and read and revised the manuscript. All authors read and approved the final manuscript.
HER-2/neu-targeted therapy has been successfully used in advanced gastric cancer, but the role of HER-2/neu in the prognosis of gastric cancer is not yet clear. In this study, we investigated the correlation between HER-2/neu expression and amplification as well as their association with clinic outcomes in patients with curatively resected gastric cancer.
We constructed tissue microarray blocks containing >70% of gastric cancer tissue and matched adjacent normal gastric tissue for 227 patients. Expression of the HER-2/neu protein in these specimens was analyzed using immunohistochemical staining. Amplification of HER-2/neu was also analyzed for the same samples using fluorescence in situ hybridization. Data on clinicopathological features and relevant prognostic factors in these patients were analyzed.
Of the 227 gastric cancer samples, 11.89% were positive for HER-2/neu overexpression/amplification under the new scoring system. HER-2/neu overexpression/amplification was closely correlated to the Lauren type, degree of differentiation, tumor size and lymph node metastasis. HER-2/neu overexpression/amplification predicted poor survival in univariate analysis but not in a Cox proportional hazards model.
HER-2/neu overexpression/amplification was not an independent predictor for survival in patients with curatively resected gastric cancer.
Chen WQ: Estimation of cancer incidence and mortality in China in 2004–2005. Zhonghua Zhong Liu Za Zhi. 2009, 31: 664-668. PubMed
Qin SQ, GX : The status quo and new progress in the chemotherapy of the advanced gastric cancer. Chin Clin Oncol. 2006, 11: 641-652.
Bang YJ, van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK, ToGA Trial Investigators: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010, 376: 687-697. 10.1016/S0140-6736(10)61121-X. CrossRefPubMed
Shitara K, Yatabe Y, Matsuo K, Sugano M, Kondo C, Takahari D, Ura T, Tajika M, Ito S, Muro K: Prognosis of patients with advanced gastric cancer by HER2 status and trastuzumab treatment. Gastric Cancer. 2012, -[Epub ahead of print]
Hung MC, Lau YK: Basic science of HER-2/neu: a review. Semin Oncol. 1999, 26: 51-59. PubMed
McKenzie SJ, DeSombre KA, Bast BS, Hollis DR, Whitaker RS, Berchuck A, Boyer CM, Bast RC: Serum levels of HER-2 neu (C-erbB-2) correlate with overexpression of p185neu in human ovarian cancer. Cancer. 1993, 71: 3942-3946. 10.1002/1097-0142(19930615)71:12<3942::AID-CNCR2820711224>3.0.CO;2-3. CrossRefPubMed
Tanner M, Hollmen M, Junttila TT, Kapanen AI, Tommola S, Soini Y, Helin H, Salo J, Joensuu H, Sihvo E, Elenius K, Isola J: Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol. 2005, 16: 273-278. 10.1093/annonc/mdi064. CrossRefPubMed
Barros-Silva JD, Leitao D, Afonso L, Vieira J, Dinis-Ribeiro M, Fragoso M, Bento MJ, Santos L, Ferreira P, Rego S, Brandão C, Carneiro F, Lopes C, Schmitt F, Teixeira MR: Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients. Br J Cancer. 2009, 100: 487-493. 10.1038/sj.bjc.6604885. PubMedCentralCrossRefPubMed
Park DI, Yun JW, Park JH, Oh SJ, Kim HJ, Cho YK, Il Sohn C, Jeon WK, Kim BI, Yoo CH, Son BH, Cho EY, Chae SW, Kim EJ, Sohn JH, Ryu SH, Sepulveda AR: HER-2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci. 2006, 51: 1371-1379. 10.1007/s10620-005-9057-1. CrossRefPubMed
Terashima M, Kitada K, Ochiai A, Ichikawa W, Kurahashi I, Sakuramoto S, Katai H, Sano T, Imamura H, Sasako M: Impact of expression of human epidermal growth factor receptors EGFR and ERBB2 on survival in stage II/III gastric cancer. Clin Cancer Res. 2012, 18: 5992-6000. 10.1158/1078-0432.CCR-12-1318. CrossRefPubMed
Kim MA, Jung EJ, Lee HS, Lee HE, Jeon YK, Yang HK, Kim WH: Evaluation of HER-2 gene status in gastric carcinoma using immunohistochemistry, fluorescence in situ hybridization, and real-time quantitative polymerase chain reaction. Hum Pathol. 2007, 38: 1386-1393. 10.1016/j.humpath.2007.02.005. CrossRefPubMed
Tubbs RR, Pettay JD, Roche PC, Stoler MH, Jenkins RB, Grogan TM: Discrepancies in clinical laboratory testing of eligibility for trastuzumab therapy: apparent immunohistochemical false-positives do not get the message. J Clin Oncol. 2001, 19: 2714-2721. PubMed
Kim KC, Koh YW, Chang HM, Kim TH, Yook JH, Kim BS, Jang SJ, Park YS: Evaluation of HER2 protein expression in gastric carcinomas: comparative analysis of 1,414 cases of whole-tissue sections and 595 cases of tissue microarrays. Ann Surg Oncol. 2011, 18: 2833-2840. 10.1245/s10434-011-1695-2. CrossRefPubMed
Begnami MDFE, Fregnani JH, Nonogaki S, Montagnini AL, Da Costa WL, Soares FA: Prognostic implications of altered human epidermal growth factor receptors (HERs) in gastric carcinomas: HER2 and HER3 are predictors of poor outcome. J Clin Oncol. 2011, 29: 3030-3036. 10.1200/JCO.2010.33.6313. CrossRefPubMed
Hsu JT, Chen TC, Tseng JH, Chiu CT, Liu KH, Yeh CN, Hwang TL, Jan YY, Yeh TS: Impact of HER-2 overexpression/amplification on the prognosis of gastric cancer patients undergoing resection: a single-center study of 1,036 patients. Oncologist. 2011, 16: 1706-1713. 10.1634/theoncologist.2011-0199. PubMedCentralCrossRefPubMed
Chung H, Bang YJ, Xu JM, Lordick F, Sawaki A, Lipatov O, Lehle M, Pickl M, Rueschoff J, van Cutsem E: 6511 Human epidermal growth factor receptor 2 (HER2) in gastric cancer (GC): results of the ToGA trial screening programme and recommendations for HER2 testing. European Journal of Cancer Supplements. 2009, 7: 364- CrossRef
Mayer B, Johnson JP, Leitl F, Jauch KW, Heiss MM, Schildberg FW, Birchmeier W, Funke I: E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res. 1993, 53: 1690-1695. PubMed
Yonemura Y, Ninomiya I, Ohoyama S, Kimura H, Yamaguchi A, Fushida S, Kosaka T, Miwa K, Miyazaki I, Endou Y, Tanaka M, Sasaki T: Expression of c-erbB-2 oncoprotein in gastric carcinoma. Immunoreactivity for c-erbB-2 protein is an independent indicator of poor short-term prognosis in patients with gastric carcinoma. Cancer. 1991, 67: 2914-2918. 10.1002/1097-0142(19910601)67:11<2914::AID-CNCR2820671134>3.0.CO;2-G. CrossRefPubMed
- Prognosis significance of HER-2/neu overexpression/amplification in Chinese patients with curatively resected gastric cancer after the ToGA clinical trial
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