Clinical Research Progress of HER-2/neu Gene in Gastric Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 JIGuo-feng ,  MAChong

Department of Gastrointestinal Surgery, Xinmin Branch of China-Japan Union Hospital, Jilin University, Changchun 130021, Jilin Province, China;

Corresponding author：

MAChong, Email: zt1983@163.com

Keywords：

Human epidermal growth factor receptor 2 gene; Gastric cancer; Targeted therapy

DOI：

10.7507/1007-9424.20150196

Video：

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Objective To summarize the biological characteristics of human epidermal growth factor receptor 2 (HER-2/neu) gene, the expression and meaning of HER-2/neu gene in gastric cancer, and clinical application of targeted medicine of HER-2/neu gene in gastric cancer. Methods Related literatures about HER-2/neu gene and gastric cancer were retrieved for a review. Results HER-2/neu gene encoded human epidermal growth factor receptor, and it participated in the gene regulation of tumor cell proliferation, invasion, and metastasis through the downstream signal transduction pathway. Amplification of HER-2/neu gene or overexpression of HER-2 was closely bound up to the occurrence and development of gastric cancer, however, whether it could be used as independent prognostic factors of gastric cancer remained to be controversial. Several targeted medicine of HER-2/neu gene had applied to clinical at present, and all of them obtained good short-term effect. Conclusion HER-2/neu gene is a reliable target of gastric cancer and targeted medicine of HER-2/neu gene has a promising prospect.

Citation： JIGuo-feng, MAChong. Clinical Research Progress of HER-2/neu Gene in Gastric Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(6): 754-758. doi: 10.7507/1007-9424.20150196 Copy

1.	Jemal A, Bray F, Center MM, et al. Globle cancer statistics. CA Cancer J Clin, 2011, 61(2):69-90.
2.	李国立, 李宁, 黎介寿.难以切除的局部进展期胃癌规范化综合治疗.中国实用外科杂志, 2014, 34(7):633-636.
3.	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, 2010, 376(9742):687-697.
4.	Fernö M, Haglund M, Bendahl PO, et al. Quality assured HER2 analysis in breast cancer. Important therapeutic predictive and prognostic factor. Lakartidningen, 2008, 105(32-33):2181-2184.
5.	Park JW, Neve RM, Szollosi J, et al. Unraveling the biologic and clinical complexities of HER2. Clin Breast Cancer, 2008, 8(5):392-401.
6.	Shepard HM, Brdlik CM, Schreiber H. Signal integration:a framework for understanding the efficacy of therapeutics targeting the human EGFR family. J Clin Invest, 2008, 118(11):3574-3581.
7.	Ben-Kasus T, Schechter B, Lavi S, et al. Persistent elimination of ErbB-2/HER2-overexpressing tumors using combinations of monoclonal antibodies:relevance of receptor endocytosis. Proc Natl Acad Sci U S A, 2009, 106(9):3294-3299.
8.	Carter WB, Hoying JB, Boswell C, et al. HER2/neu over-expression induces endothelial cell retraction. Int J Cancer, 2001, 91(3):295-299.
9.	Tan M, Li P, Klos KS, et al. ErbB2 promotes Src synthesis and stability:novel mechanisms of Src activation that confer breast cancer metastasis. Cancer Res, 2005, 65(5):1858-1867.
10.	Sliwkowski MX, Lofgren JA, Lewis GD, et al. Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). Semin Oncol, 1999, 26(4 Suppl 12):60-70.
11.	Lee HS, Park CK, Oh E, et al. Low SP1 expression differentially affects intestinal-type compared with diffuse-type gastric adenocarcinoma. PLoS One, 2013, 8(2):e55522.
12.	刘彩云, 寿成超.乳腺癌患者血清HER-2/neu胞外域的临床意义.国际检验医学杂志, 2006, 27(3):237-239.
13.	钟山, 余英豪, 黄红浪, 等.荧光原位杂交法对胃癌组织HER-2基因状态的检测.世界华人消化杂志, 2011, 19(2):132-137.
14.	Jacquemier J, Spyratos F, Esterni B, et al. SISH/CISH or qPCR as alternative techniques to FISH for determination of HER2 amplification status on breast tumors core needle biopsies:a multicenter experience based on 840 cases. BMC Cancer, 2013, 13:351.
15.	Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer:American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch Pathol Lab Med, 2014, 138(2):241-256.
16.	Sakai K, Mori S, Kawamoto T, et al. Expression of epidermal growth factor receptors on normal human gastric epithelia and gastric carcinomas. J Natl Cancer Inst, 1986, 77(5):1047-1052.
17.	Hirashima N, Takahashi W, Yoshii S, et al. Protein overexpression and gene amplification of c-erb B-2 in pulmonary carcinomas:a comparative immunohistochemical and fluorescence in situ hybridization study. Mod Pathol, 2001, 14(6):556-562.
18.	Tanner M, Hollmén M, Junttila TT, et al. Amplification of HER-2 in gastric carcinoma:association with TopoisomeraseⅡalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol, 2005, 16(2):273-278.
19.	刘俊林, 李振凯, 信芳杰, 等.胃癌HER2蛋白表达及基因扩增分析.中华胃肠外科杂志, 2013, 16(9):898-901.
20.	HER-2研究全国协作组.胃癌中HER-2/neu基因扩增和蛋白表达的多中心研究.中华消化杂志, 2006, 26(10):657-660.
21.	Jørgensen JT. Targeted HER2 treatment in advanced gastric cancer. Oncology, 2010, 78(1):26-33.
22.	Bang Y, Chung H, Xu J, et al. Pathological features of advanced gastric cancer (GC):relationship to human epidermal growth factor receptor 2 (HER2) positivity in the global screening programme of the ToGA trial. J Clin Oncol, 2009, 27(15S):LBA4556.
23.	Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer:results from a validation study. Histopathology, 2008, 52(7):797-805.
24.	Jørgensen JT, Hersom M. HER2 as a prognostic marker in gastric cancer-a systematic analysis of data from the literature. J Cancer, 2012, 3:137-144.
25.	Kim KC, Koh YW, Chang HM, et al. 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(10):2833-2840.
26.	Dang HZ, Yu Y, Jiao SC. Prognosis of HER2 over-expressing gastric cancer patients with liver metastasis. World J Gastroenterol, 2012, 18(19):2402-2407.
27.	武鸿美, 刘艳辉, 林锋, 等.中国胃癌患者HER2蛋白表达与临床病理学参数及预后的关系.中华病理学杂志, 2011, 40(5):296-299.
28.	Okines AF, Thompson LC, Cunningham D, et al. Effect of HER2 on prognosis and benefit from peri-operative chemotherapy in early oesophago-gastric adenocarcinoma in the MAGIC trial. Ann Oncol, 2013, 24(5):1253-1261.
29.	Sheng WQ, Huang D, Ying JM, et al. HER2 status in gastric cancers:a retrospective analysis from four Chinese representative clinical centers and assessment of its prognostic significance. Ann Oncol, 2013, 24(9):2360-2364.
30.	Chua TC, Merrett ND. Clinicopathologic factors associated with HER2-positive gastric cancer and its impact on survival outcomes-a systematic review. Int J Cancer, 2012, 130(12):2845-2856.
31.	Okines AF, Cunningham D. Trastuzumab in gastric cancer. Eur J Cancer, 2010, 46(11):1949-1959.
32.	Tinoco G, Warsch S, Glück S, et al. Treating breast cancer in the 21^st century:emerging biological therapies. J Cancer, 2013, 4(2):117-132.
33.	Davison DL, Patel K, Chawla LS. Hemodynamic monitoring in the critically ill:spanning the range of kidney function. Am J Kidney Dis, 2012, 59(5):715-723.
34.	Iwamoto Y, Tamai A, Kohno K, et al. Usefulness of respiratory variation of inferior vena cava diameter for estimation of elevated central venous pressure in children with cardiovascular disease. Circ J, 2011, 75(5):1209-1214.
35.	Albanell J, Montagut C, Jones ET, et al. A phaseⅠstudy of the safety and pharmacokinetics of the combination of pertuzumab (rhuMab 2C4) and capecitabine in patients with advanced solid tumors. Clin Cancer Res, 2008, 14(9):2726-2731.
36.	Chen CT, Kim H, Liska D, et al. Met activation mediates resistance to lapatinib inhibition of HER2-amplified gastric cancer cells. Mol Cancer Ther, 2012, 11(3):660-669.
37.	Cameron D, Casey M, Press M, et al. A phaseⅢrandomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab:updated efficacy and biomarker analyses. Breast Cancer Res Treat, 2008, 112(3):533-543.
38.	Iqbal S, Goldman B, Lenz HJ, et al. S0413:a phaseⅡSWOG study of GW572016 (lapatinib) as first line therapy in patients (pts) with advanced or metastatic gastric cancer. J Clin Oncol, 2007, 25(18S):LBA4621.
39.	Hecht JR, Bang YJ, Qin SK, et al. Lapatinib in combination with capecitabine plus oxaliplatin (CapeOx) in HER2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma (AC):The TRIO-013/LOGiC Trial. J Clin Oncol, 2013, 31(18S):LBA4001.
40.	Moelans CB, Milne AN, Morsink FH, et al. Low frequency of HER2 amplification and overexpression in early onset gastric cancer. Cell Oncol (Dordr), 2011, 34(2):89-95.

1. Jemal A, Bray F, Center MM, et al. Globle cancer statistics. CA Cancer J Clin, 2011, 61(2):69-90.
2. 李国立, 李宁, 黎介寿.难以切除的局部进展期胃癌规范化综合治疗.中国实用外科杂志, 2014, 34(7):633-636.
3. 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, 2010, 376(9742):687-697.
4. Fernö M, Haglund M, Bendahl PO, et al. Quality assured HER2 analysis in breast cancer. Important therapeutic predictive and prognostic factor. Lakartidningen, 2008, 105(32-33):2181-2184.
5. Park JW, Neve RM, Szollosi J, et al. Unraveling the biologic and clinical complexities of HER2. Clin Breast Cancer, 2008, 8(5):392-401.
6. Shepard HM, Brdlik CM, Schreiber H. Signal integration:a framework for understanding the efficacy of therapeutics targeting the human EGFR family. J Clin Invest, 2008, 118(11):3574-3581.
7. Ben-Kasus T, Schechter B, Lavi S, et al. Persistent elimination of ErbB-2/HER2-overexpressing tumors using combinations of monoclonal antibodies:relevance of receptor endocytosis. Proc Natl Acad Sci U S A, 2009, 106(9):3294-3299.
8. Carter WB, Hoying JB, Boswell C, et al. HER2/neu over-expression induces endothelial cell retraction. Int J Cancer, 2001, 91(3):295-299.
9. Tan M, Li P, Klos KS, et al. ErbB2 promotes Src synthesis and stability:novel mechanisms of Src activation that confer breast cancer metastasis. Cancer Res, 2005, 65(5):1858-1867.
10. Sliwkowski MX, Lofgren JA, Lewis GD, et al. Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). Semin Oncol, 1999, 26(4 Suppl 12):60-70.
11. Lee HS, Park CK, Oh E, et al. Low SP1 expression differentially affects intestinal-type compared with diffuse-type gastric adenocarcinoma. PLoS One, 2013, 8(2):e55522.
12. 刘彩云, 寿成超.乳腺癌患者血清HER-2/neu胞外域的临床意义.国际检验医学杂志, 2006, 27(3):237-239.
13. 钟山, 余英豪, 黄红浪, 等.荧光原位杂交法对胃癌组织HER-2基因状态的检测.世界华人消化杂志, 2011, 19(2):132-137.
14. Jacquemier J, Spyratos F, Esterni B, et al. SISH/CISH or qPCR as alternative techniques to FISH for determination of HER2 amplification status on breast tumors core needle biopsies:a multicenter experience based on 840 cases. BMC Cancer, 2013, 13:351.
15. Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer:American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch Pathol Lab Med, 2014, 138(2):241-256.
16. Sakai K, Mori S, Kawamoto T, et al. Expression of epidermal growth factor receptors on normal human gastric epithelia and gastric carcinomas. J Natl Cancer Inst, 1986, 77(5):1047-1052.
17. Hirashima N, Takahashi W, Yoshii S, et al. Protein overexpression and gene amplification of c-erb B-2 in pulmonary carcinomas:a comparative immunohistochemical and fluorescence in situ hybridization study. Mod Pathol, 2001, 14(6):556-562.
18. Tanner M, Hollmén M, Junttila TT, et al. Amplification of HER-2 in gastric carcinoma:association with TopoisomeraseⅡalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol, 2005, 16(2):273-278.
19. 刘俊林, 李振凯, 信芳杰, 等.胃癌HER2蛋白表达及基因扩增分析.中华胃肠外科杂志, 2013, 16(9):898-901.
20. HER-2研究全国协作组.胃癌中HER-2/neu基因扩增和蛋白表达的多中心研究.中华消化杂志, 2006, 26(10):657-660.
21. Jørgensen JT. Targeted HER2 treatment in advanced gastric cancer. Oncology, 2010, 78(1):26-33.
22. Bang Y, Chung H, Xu J, et al. Pathological features of advanced gastric cancer (GC):relationship to human epidermal growth factor receptor 2 (HER2) positivity in the global screening programme of the ToGA trial. J Clin Oncol, 2009, 27(15S):LBA4556.
23. Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer:results from a validation study. Histopathology, 2008, 52(7):797-805.
24. Jørgensen JT, Hersom M. HER2 as a prognostic marker in gastric cancer-a systematic analysis of data from the literature. J Cancer, 2012, 3:137-144.
25. Kim KC, Koh YW, Chang HM, et al. 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(10):2833-2840.
26. Dang HZ, Yu Y, Jiao SC. Prognosis of HER2 over-expressing gastric cancer patients with liver metastasis. World J Gastroenterol, 2012, 18(19):2402-2407.
27. 武鸿美, 刘艳辉, 林锋, 等.中国胃癌患者HER2蛋白表达与临床病理学参数及预后的关系.中华病理学杂志, 2011, 40(5):296-299.
28. Okines AF, Thompson LC, Cunningham D, et al. Effect of HER2 on prognosis and benefit from peri-operative chemotherapy in early oesophago-gastric adenocarcinoma in the MAGIC trial. Ann Oncol, 2013, 24(5):1253-1261.
29. Sheng WQ, Huang D, Ying JM, et al. HER2 status in gastric cancers:a retrospective analysis from four Chinese representative clinical centers and assessment of its prognostic significance. Ann Oncol, 2013, 24(9):2360-2364.
30. Chua TC, Merrett ND. Clinicopathologic factors associated with HER2-positive gastric cancer and its impact on survival outcomes-a systematic review. Int J Cancer, 2012, 130(12):2845-2856.
31. Okines AF, Cunningham D. Trastuzumab in gastric cancer. Eur J Cancer, 2010, 46(11):1949-1959.
32. Tinoco G, Warsch S, Glück S, et al. Treating breast cancer in the 21^st century:emerging biological therapies. J Cancer, 2013, 4(2):117-132.
33. Davison DL, Patel K, Chawla LS. Hemodynamic monitoring in the critically ill:spanning the range of kidney function. Am J Kidney Dis, 2012, 59(5):715-723.
34. Iwamoto Y, Tamai A, Kohno K, et al. Usefulness of respiratory variation of inferior vena cava diameter for estimation of elevated central venous pressure in children with cardiovascular disease. Circ J, 2011, 75(5):1209-1214.
35. Albanell J, Montagut C, Jones ET, et al. A phaseⅠstudy of the safety and pharmacokinetics of the combination of pertuzumab (rhuMab 2C4) and capecitabine in patients with advanced solid tumors. Clin Cancer Res, 2008, 14(9):2726-2731.
36. Chen CT, Kim H, Liska D, et al. Met activation mediates resistance to lapatinib inhibition of HER2-amplified gastric cancer cells. Mol Cancer Ther, 2012, 11(3):660-669.
37. Cameron D, Casey M, Press M, et al. A phaseⅢrandomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab:updated efficacy and biomarker analyses. Breast Cancer Res Treat, 2008, 112(3):533-543.
38. Iqbal S, Goldman B, Lenz HJ, et al. S0413:a phaseⅡSWOG study of GW572016 (lapatinib) as first line therapy in patients (pts) with advanced or metastatic gastric cancer. J Clin Oncol, 2007, 25(18S):LBA4621.
39. Hecht JR, Bang YJ, Qin SK, et al. Lapatinib in combination with capecitabine plus oxaliplatin (CapeOx) in HER2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma (AC):The TRIO-013/LOGiC Trial. J Clin Oncol, 2013, 31(18S):LBA4001.
40. Moelans CB, Milne AN, Morsink FH, et al. Low frequency of HER2 amplification and overexpression in early onset gastric cancer. Cell Oncol (Dordr), 2011, 34(2):89-95.

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Clinical Research Progress of HER-2/neu Gene in Gastric Cancer

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