HER2 mRNA Status Contributes to the Discrepancy Between Gene Amplification and Protein Overexpression in Gastric Cancer

• Published in: Digestive diseases and sciences Vol. 59; no. 2; pp. 328 - 335
• Main Authors: Ma, Gui-Fen, Liu, Yi-Mei, Gao, Hong, Miao, Qing, Luo, Tian-Cheng, Zeng, Xiao-Qing, Chen, Shi-Yao
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.02.2014; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Analysis; Biochemistry; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer; Case-Control Studies; Cell Line, Tumor; Coculture Techniques; Epidermal growth factor; Female; Fluorescence; Gastroenterology; Gene Amplification; Gene Expression Regulation, Neoplastic; Genes; Genetic aspects; Hepatology; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Leukocytes, Mononuclear - metabolism; Male; Matrix Metalloproteinase 9 - genetics; Medicine; Medicine & Public Health; Messenger RNA; Middle Aged; Oncology; Original Article; Predictive Value of Tests; Real-Time Polymerase Chain Reaction; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; RNA, Messenger - metabolism; Smad7 Protein - genetics; Stomach cancer; Stomach Neoplasms - enzymology; Stomach Neoplasms - genetics; Transplant Surgery; Up-Regulation; Coculture; Matrix metalloproteinase 9; HER2; Gastric cancer; Smad7
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-013-2925-1

Background Human epidermal growth factor receptor 2 (HER2) is an important proto-oncogene of prognostic use in gastric cancer (GC). Fluorescence in-situ hybridization (FISH) and immunohistochemistry (IHC) are the main clinical methods of detection of HER2, but consistency between the methods is poor and the cause of the discrepancy is unclear. Aim To investigate the involvement of HER2 mRNA status in the disparity between gene amplification and protein overexpression. Methods We investigated HER2 gene, mRNA, and protein profiles in gastric precancer and cancer tissues by use of the molecular approaches FISH, real-time polymerase chain reaction, and IHC. The relationships between HER2 and matrix metalloproteinase 9 (MMP9) and Smad7 expression were analyzed and the involvement of HER2 in the interaction between tumor cells and lymphocytes was investigated by coculturing GC cell lines with peripheral blood mononuclear cells (PBMCs). Results HER2 protein expression was significantly increased in cancer compared with precancer ( P  = 0.003), and the corresponding mRNA levels were significantly lower in precancer and cancer tissues than in normal tissues ( κ  = 0.290, P  = 0.025). HER2 mRNA levels were significantly higher in tumor than in peritumor tissue ( P  = 0.028), and were positively correlated with MMP9 and Smad7 mRNA levels in tumor tissues. HER2 mRNA expression in GC cell lines was increased by coculture with PBMCs. Conclusions Different HER2 mRNA profiles, possibly in relation to contact between tumor cells and lymphocytes, might help to explain the discrepancy between gene amplification and protein overexpression results.