Human epidermal growth factor receptor 2 (Erbb2/HER2) overexpression, which was previously detected in invasive breast cancer, has now been implicated in advanced gastric cancer (GC) and gastroesophageal junction cancer (GEC). A study was conducted to determine the rate of HER2 positivity in patients with locally advanced or metastatic GC and GEC in Malaysia and to assess the impact of various demographic and clinical parameters on HER2 positivity.
A total of 228 adult patients with GC or GEC were enrolled from Subang Jaya Medical Centre, Malaysia, for retrospective (210) and prospective study. All patients were subjected to the HER2 immunohistochemistry test using an FDA-approved, standardized test kit. Carcinomas scoring 2+ on immunohistochemistry were further tested with HER2 in situ hybridization (ISH) using an FDA-approved test kit.
The overall rate of HER2 positivity in the population studied was 24.6% (n = 56). The rate was significantly higher in men than in women (29.6 vs. 16.3%; p = 0.024). HER2 overexpression was significantly more common in diffuse type than in intestinal type of tumors (39.8 vs. 14.9%; p < 0.001). In our study, out of 56 samples, 44 (78.6%) were considered for gene amplification testing, out of which 40 (90.1%) samples showed gene amplification. There was no statistically significant correlation between HER2 positivity and patient age, race, tumor location, tumor differentiation, and TNM staging.
HER2 overexpression was evident in nearly 25% of the Malaysian patients with locally advanced or metastatic gastric cancer. The overexpression correlated significantly with male gender and diffuse-type tumors. The majority of the IHC-positive tumors demonstrated c-erb2 gene amplification and this finding reached statistical significance.
International Agency for Research on Cancer. Available at http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx Accessed on November 02, 2015.
Malaysian cancer statistics—data and figure. Peninsular Malaysia 2006. Available at http://www.moh.gov.my/images/gallery/Report/Cancer/MalaysiaCancerStatistics_2006 . pdf Accessed on November 02, 2015.
Uedo N. Screening patients for gastric cancer: art and science are better together. Annals Gastroenterol. 2014;27:1–2.
Yildirim M, Sezgin A, Dilli UD, Suren D, Yıldız M, Kaya V, et al. Prognostic and predictive role of HER2 expression in metastatic gastric cancer in Turkish patient. Cancer Res J. 2013;1:20–5. CrossRef
Hecht JR, Bang YJ, Shukui K, et al. Lapatinib in combination with capecitabine plus oxaliplatin in human epidermal growth factor receptor 2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma: TRIO-013/LOGiC—a randomized phase III trial. JCO. 2016;34(5):443–51. CrossRef
Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki 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. 2010;376:687–97. CrossRefPubMed
European Medicines Agency (2009). Post-authorisation summary of positive opinion* for HERCEPTIN. Available at http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion/human/000278/WC500059913.pdf Accessed on November 02, 2015
Narita T, Seshimo A, Suzuki M, Murata J, Kameoka S. Status of tissue expression and serum levels of HER2 in gastric cancer patients in Japan. Hepatogastroenterol. 2013;60:1083–8.
National Cancer Registry Report. Malaysia cancer statistics—data and figure 2007 Ministry of Health Malaysia. Available at http://www.care.upm.edu.my/dokumen/13603_NCR2007.pdf Accessed on November 02, 2015.
Iqbal N, Iqbal N. Human epidermal growth factor receptor 2 (HER2) in cancers: overexpression and therapeutic implications. Molecular Biology Int. 2014; doi: 10.1155/2014/852748.
Yano T, Doi T, Ohtsu A, Boku N, Hashizume K, Nakanishi M, et al. Comparison of HER2 gene amplification assessed by fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer. Oncol Rep. 2006;15:65–71. PubMed
Rajgopal I, Niveditha SR, Sahadev R, Nagappa PK, Rajendra SG. HER 2 expression in gastric and gastro-esophageal junction (GEJ) adenocarcinomas. J Clin & Diag Res. 2015;9:EC06–10.
Shan L, Ying J, Lu N. HER2 expression and relevant clinicopathological features in gastric and gastroesophageal junction adenocarcinoma in a Chinese population. Diagc Pathol. 2013;8:76.
JanjigianYY WD, Pauligk C, Steinmetz K, et al. Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA international collaborative analysis. Ann Oncol. 2012; doi: 10.1093/annonc/mds104.
Terashima M, Ochiai A, Kitada K, et al. Impact of human epidermal growth factor receptor (EGFR) and ERBB2 (HER2) expressions on survival in patients with stage II/III gastric cancer, enrolled in the ACTS-GC study. J Clin Oncol. 2011;29:4013. CrossRef
- Prevalence of HER2 Positivity and Its Clinicopathological Correlation in Locally Advanced/Metastatic Gastric Cancer Patients in Malaysia
Ho Kean Fatt
Foo Yoke Ching
- Springer US
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