Detection of Her‑2/neu expression in gastric cancer: Quantitative PCR versus immunohistochemistry

Zhu,Guang‑Jun; Xu,Chun‑Wei; Fang,Mei‑Yu; Zhang,Yu‑Ping; Li,Yang

doi:10.3892/etm.2014.1982

Detection of Her‑2/neu expression in gastric cancer: Quantitative PCR versus immunohistochemistry

Authors:
- Guang‑Jun Zhu
- Chun‑Wei Xu
- Mei‑Yu Fang
- Yu‑Ping Zhang
- Yang Li
View Affiliations

Affiliations: Department of Central Laboratory, The 281st Hospital of the PLA, Qinhuangdao, Hebei 066105, P.R. China, Department of Pathology, The General Military Hospital of Beijing PLA, Beijing 100700, P.R. China, Department of Integrated Chinese Traditional Medicine and Western Medicine, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310021, P.R. China, Department of Pathology, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China, Department of Oncology, The General Military Hospital of Beijing PLA, Beijing 100700, P.R. China
Published online on: September 22, 2014 https://doi.org/10.3892/etm.2014.1982
Pages: 1501-1507

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of this study was to compare quantitative polymerase chain reaction (qPCR) with immunohistochemistry (IHC) for the detection of Her‑2 in gastric cancer, and to investigate the correlation between the expression levels of human epidermal growth factor receptor 2 (Her‑2) and clinical features. Clinical data from 426 cases of gastric cancer were collected. Her‑2 expression levels in cancerous tissue were detected using IHC, and the Her‑2/neu gene expression levels were determined by qPCR. The correlation between the expression level of Her‑2 and clinical features was investigated. The positive expression rate of Her‑2 in cancerous tissue detected using qPCR and IHC was 11.17% (46/412) and 13.38% (57/426), respectively. The positive expression of the Her‑2 protein/gene was significantly correlated with the depth of invasion and lymphatic metastasis, as well as the TNM stage (P<0.05). No significant correlation was identified between positive expression of the Her‑2 protein/gene and tumor location, age, gender, differentiation degree and Lauren classification (P>0.05). The diagnostic consistency was good between the two methods (κ=0.828). The results indicate that the expression of Her‑2/neu is closely associated with the development of gastric cancer. qPCR is a convenient, objective and efficient method, which may be used as an alternative to IHC or fluorescence in situ hybridization for the detection of Her‑2/neu gene.

View Figures

View References

1	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar
2	Jemal A, Bray F, Center MM, et al: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar
3	Ferlay J, Shin HR, Bray F, et al: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar : PubMed/NCBI
4	Zou XN, Duan JJ, Huangfu XM, Chen WQ and Zhao P: Analysis of stomach cancer mortality in the national retrospective sampling survey of death causes in China. Chin J Prev Med. 44:390–397. 2010.(In Chinese).
5	Arteaga C: Targeting Her1/EGFR: a molecular approach to cancer therapy. Semin Oncol. 30(Suppl 7): 3–14. 2003. View Article : Google Scholar : PubMed/NCBI
6	Park DI, Yun JW, Park JH, et al: Her-2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci. 51:1371–1379. 2006. View Article : Google Scholar : PubMed/NCBI
7	Hamilton SR and Aaltonen LA: World Health Organization classification of tumors. Pathology and Genetics of Tumours of the Digestive System. IARC Press; Lyon, France: pp. 265–314. 2000
8	Ichikura T, Tomimatsu S, Uefuji K, et al: Evaluation of the New American Joint Committee on Cancer/International Union against cancer classification of lymph node metastasis from gastric carcinoma in comparison with the Japanese classification. Cancer. 86:553–558. 1999. View Article : Google Scholar
9	Moelans CB, van Diest PJ, Milne AN and Offerhaus GJ: Her-2/neu testing and therapy in gastroesophageal adenocarcinoma. Patholog Res Int. 2011:6741822010.PubMed/NCBI
10	Casalini P, Iorio MV, Galmozzi E and Ménard S: Role of HER receptors family in development and differentiation. J Cell Physiol. 200:343–350. 2004. View Article : Google Scholar : PubMed/NCBI
11	Gravalos C and Jimeno A: HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol. 19:1523–1529. 2008. View Article : Google Scholar : PubMed/NCBI
12	Wolff AC, Hammond ME, Schwartz JN, et al: American Society of Clinical Oncology/College of American Pathologists: American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med. 131:18–43. 2007.
13	Bang YJ, Van Cutsem E, Feyereislova A, et al: 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. 376:687–697. 2010. View Article : Google Scholar
14	Hayes DF, Yamauchi H, Broadwater G, et al: Cancer and Leukemia Group B: Circulating Her-2/erbB-2/c-neu (Her-2) extracellular domain as a prognostic factor in patients with metastatic breast cancer: Cancer and Leukemia Group B Study 8662. Clin Cancer Res. 7:2703–2711. 2001.PubMed/NCBI
15	Tsugawa K, Yonemura Y, Hirono Y, et al: Amplification of the c-met, c-erbB-2 and epidermal growth factor receptor gene in human gastric cancers: correlation to clinical features. Oncology. 55:475–481. 1998. View Article : Google Scholar : PubMed/NCBI
16	Yonemura Y, Ninomiya I, Tsugawa K, et al: Prognostic significance of c-erbB-2 gene expression in the poorly differentiated type of adenocarcinoma of the stomach. Cancer Detect Prev. 22:139–146. 1998. View Article : Google Scholar : PubMed/NCBI
17	Yonemura Y, Ninomiya I, Yamaguchi A, et al: Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric cancer. Cancer Res. 51:1034–1038. 1991.PubMed/NCBI
18	Uchino S, Tsuda H, Maruyama K, et al: Overexpression of c-erbB-2 protein in gastric cancer. Its correlation with long-term survival of patients. Cancer. 72:3179–3184. 1993. View Article : Google Scholar : PubMed/NCBI
19	Barberis M, Pellegrini C, Cannone M, et al: Quantitative PCR and Her2 testing in breast cancer: a technical and cost-effectiveness analysis. Am J Clin Pathol. 129:563–570. 2008. View Article : Google Scholar : PubMed/NCBI
20	Bossard C, Bieche I, Le Doussal V, Lidereau R and Sabourin JC: Real-time RT-PCR: a complementary method to detect Her-2 status in breast carcinoma. Anticancer Res. 25:4679–4683. 2005.PubMed/NCBI
21	Tse C, Brault D, Gligorov J, et al: Evaluation of the quantitative analytical methods real-time PCR for Her-2 gene quantification and ELISA of serum Her-2 protein and comparison with fluorescence in situ hybridization and immunohistochemistry for determining Her-2 status in breast cancer patients. Clin Chem. 51:1093–1101. 2005.
22	Nistor A, Watson PH, Pettigrew N, et al: Real-time PCR complements immunohistochemistry in the determination of Her-2/neu status in breast cancer. BMC Clin Pathol. 6:22006. View Article : Google Scholar : PubMed/NCBI
23	Chariyalertsak S, Purisa W and Vinyuvat S: Her-2/neu amplification determined by real-time quantitative PCR and its association with clinical outcome of breast cancer in Thailand. Asian Pac J Cancer Prev. 12:1703–1706. 2011.PubMed/NCBI
24	Page K, Hava N, Ward B, et al: Detection of Her2 amplification in circulating free DNA in patients with breast cancer. Br J Cancer. 104:1342–1348. 2011. View Article : Google Scholar : PubMed/NCBI