Correlation of human epidermal growth factor receptor 2 amplification with clinicopathological characteristics and prognosis of colorectal cancer patients: a meta-analysis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

YU Jiaojiao ¹ ,  YAO Nan ² , JIANG Lei ² , WANG Jun ² , WANG Likang ¹

1. The First School of Clinical Medicine of Lanzhou University, Lanzhou 730000, P. R. China;
2. Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, P. R. China;

Corresponding author：

YAO Nan, Email: 2621218399@qq.com

Keywords：

colorectal neoplasm; human epidermal growth factor receptor 2; prognosis; meta-analysis

DOI：

10.7507/1007-9424.202012085

Video：

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Objective To systematically evaluate the correlation of amplification of human epidermal growth factor receptor 2 (HER2) with the clinicopathological characteristics and prognosis of colorectal cancer patients.Methods PubMed, EMbase, Cochrane Library, Chinese Biomedical Literature Database (CBM), Wanfang, and other databases were searched, and cohort studies focused on the relationship between HER2 amplification and clinicopathological characteristics and prognosis of colorectal cancer patients were included. The retrieval time limit was from October 2020, and RevMan 5.4 software was used for meta-analysis.Results A total of 9 studies (11 cohorts) were included for meta-analysis of 7 209 patients with colorectal cancer. Results of the meta-analysis showed that HER2 amplification was not associated with overall survival [HR=1.10, 95%CI (0.98, 1.24), P=0.11]. HER2 amplification was not correlated with gender [OR=0.98, 95%C1 (0.74, 1.31), P=0.90] and tumor differentiation [OR=0.80, 95%C1 (0.49, 1.32), P=0.39], but correlated with the tumor location [OR=1.85, 95%C1 (1.01, 3.37), P=0.04], RAS wild-type gene [OR=6.36, 95%C1 (3.41, 11.87), P<0.000 01], TNM stage [OR=0.45, 95%C1 (0.32, 0.64), P<0.000 01], lymph node metastasis [OR=1.54, 95%C1 (1.12, 2.13), P=0.008], and the depth of tumor invasion [OR=0.17, 95%C1 (0.05, 0.55), P=0.003].Conclusion Current evidence shows that HER2 amplification is not associated with OS in patients with colorectal cancer, but associated with tumor infiltration, lymph node metastasis, TNM stage, tumor site, and RAS genotype.

Citation： YU Jiaojiao, YAO Nan, JIANG Lei, WANG Jun, WANG Likang. Correlation of human epidermal growth factor receptor 2 amplification with clinicopathological characteristics and prognosis of colorectal cancer patients: a meta-analysis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(9): 1200-1208. doi: 10.7507/1007-9424.202012085 Copy

1.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2.	Ng K, Zhu AX. Targeting the epidermal growth factor receptor in metastatic colorectal cancer. Crit Rev Oncol Hematol, 2008, 65(1): 8-20.
3.	Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet, 2014, 383(9927): 1490-1502.
4.	Nikolouzakis TK, Vassilopoulou L, Fragkiadaki P, et al. Improving diagnosis, prognosis and prediction by using biomarkers in CRC patients (Review). Oncol Rep, 2018, 39(6): 2455-2472.
5.	Wu XX, Yue GG, Dong JR, et al. Actein inhibits tumor growth and metastasis in HER2-positive breast tumor bearing mice via suppressing AKT/mTOR and Ras/Raf/MAPK signaling pathways. Front Oncol, 2020, 10: 854.
6.	Guo X, Zhou N, Chen Z, et al. Construction of ¹²⁴I-trastuzumab for noninvasive PET imaging of HER2 expression: from patient-derived xenograft models to gastric cancer patients. Gastric Cancer, 2020, 23(4): 614-626.
7.	胥润, 杜正贵. HER-2 阳性乳腺癌抗 HER-2 双靶向治疗的研究进展. 中国普外基础与临床杂志, 2021, 28(4): 544-550.
8.	Siena S, Sartore-Bianchi A, Marsoni S, et al. Targeting the human epidermal growth factor receptor 2 (HER2) oncogene in colorectal cancer. Ann Oncol, 2018, 29(5): 1108-1119.
9.	Tierney JF, Stewart LA, Ghersi D, et al. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials, 2007, 8: 16.
10.	Seo AN, Kwak Y, Kim DW, et al. HER2 status in colorectal cancer: its clinical significance and the relationship between HER2 gene amplification and expression. PLoS One, 2014, 9(5): e98528.
11.	Stahler A, Heinemann V, Neumann J, et al. Prevalence and influence on outcome of HER2/neu, HER3 and NRG1 expression in patients with metastatic colorectal cancer. Anticancer Drugs, 2017, 28(7): 717-722.
12.	Meng X, Wang R, Huang Z, et al. Human epidermal growth factor receptor-2 expression in locally advanced rectal cancer: association with response to neoadjuvant therapy and prognosis. Cancer Sci, 2014, 105(7): 818-824.
13.	Zhang X, Wu J, Wang L, et al. HER2 and BRAF mutation in colorectal cancer patients: a retrospective study in Eastern China. PeerJ, 2020, 8: e8602.
14.	Wang XY, Zheng ZX, Sun Y, et al. Significance of HER2 protein expression and HER2 gene amplification in colorectal adenocarcinomas. World J Gastrointest Oncol, 2019, 11(4): 335-347.
15.	Ingold Heppner B, Behrens HM, Balschun K, et al. HER2/neu testing in primary colorectal carcinoma. Br J Cancer, 2014, 111(10): 1977-1984.
16.	Liu F, Ren C, Jin Y, et al. Assessment of two different HER2 scoring systems and clinical relevance for colorectal cancer. Virchows Arch, 2020, 476(3): 391-398.
17.	Nam SK, Yun S, Koh J, et al. BRAF, PIK3CA, and HER2 oncogenic alterations according to KRAS mutation status in advanced colorectal cancers with distant metastasis. PLoS One, 2016, 11(3): e0151865.
18.	Richman SD, Southward K, Chambers P, et al. HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3 256 patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials. J Pathol, 2016, 238(4): 562-570.
19.	Gutierrez C, Schiff R. HER2: biology, detection, and clinical implications. Arch Pathol Lab Med, 2011, 135(1): 55-62.
20.	Pyo JS, Kang G, Park K. Clinicopathological significance and diagnostic accuracy of HER2 immunohistochemistry in colorectal cancer: a meta-analysis. Int J Biol Markers, 2016, 31(4): e389-e394.
21.	Bartley AN, Washington MK, Colasacco C, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: Guideline from the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J Clin Oncol, 2017, 35(4): 446-464.
22.	Valtorta E, Martino C, Sartore-Bianchi A, et al. Assessment of a HER2 scoring system for colorectal cancer: results from a validation study. Mod Pathol, 2015, 28(11): 1481-1491.
23.	Sartore-Bianchi A, Amatu A, Porcu L, et al. HER2 positivity predicts unresponsiveness to EGFR-targeted treatment in metastatic colorectal cancer. Oncologist, 2019, 24(10): 1395-1402.
24.	Laurent-Puig P, Balogoun R, Cayre A, et al. ERBB2 alterations a new prognostic biomarker in stage Ⅲ colon cancer from a FOLFOX based adjuvant trial (PETACC8). Ann Oncol, 2016, 27(6): 149-206.
25.	Sun SJ, Lin Q, Sun Q, et al. High HER-2 protein levels correlate with clinicopathological features in colorectal cancer. J Cancer Res Ther, 2016, 12(1): 323-333.
26.	Wu SW, Ma CC, Li WH. Does overexpression of HER-2 correlate with clinicopathological characteristics and prognosis in colorectal cancer? Evidence from a meta-analysis. Diagn Pathol, 2015, 10: 144.
27.	Li C, Liu DR, Ye LY, et al. HER-2 overexpression and survival in colorectal cancer: a meta-analysis. J Zhejiang Univ Sci B, 2014, 15(6): 582-589.
28.	Marx AH, Burandt EC, Choschzick M, et al. Heterogenous high-level HER-2 amplification in a small subset of colorectal cancers. Hum Pathol, 2010, 41(11): 1577-1585.
29.	Missiaglia E, Jacobs B, D’Ario G, et al. Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. Ann Oncol, 2014, 25(10): 1995-2001.
30.	Siena S, Sartore-Bianchi A, Trusolino L, et al. Final results of the HERACLES trial in HER2 amplified colorectal cancer. Ann Oncol, 2016, 27(Supplement 4): iv39-iv54.
31.	Wei Q, Zhang Y, Gao J, et al. Clinicopathologic characteristics of HER2-positive metastatic colorectal cancer and detection of HER2 in plasma circulating tumor DNA. Clin Colorectal Cancer, 2019, 18(3): 175-182.
32.	Schuell B, Gruenberger T, Scheithauer W, et al. HER 2/neu protein expression in colorectal cancer. BMC Cancer, 2006, 6: 123.
33.	Raghav K, Loree JM, Morris JS, et al. Validation of HER2 amplification as a predictive biomarker for anti–epidermal growth factor receptor antibody therapy in metastatic colorectal cancer. JCO Precision Oncology, 2019, 3(3): 1-13.
34.	Dong Z, Kong L, Wan Z, et al. Somatic mutation profiling and HER2 status in KRAS-positive Chinese colorectal cancer patients. Sci Rep, 2019, 9(1): 16894.
35.	Li QH, Wang YZ, Tu J, et al. Anti-EGFR therapy in metastatic colorectal cancer: mechanisms and potential regimens of drug resistance. Gastroenterol Rep (Oxf), 2020, 8(3): 179-191.
36.	Meric-Bernstam F, Hurwitz H, Raghav KPS, et al. Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol, 2019, 20(4): 518-530.
37.	陈功. 2019 年结直肠癌治疗进展盘点. 肿瘤综合治疗电子杂志, 2020, 1(6): 89-90.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Ng K, Zhu AX. Targeting the epidermal growth factor receptor in metastatic colorectal cancer. Crit Rev Oncol Hematol, 2008, 65(1): 8-20.
3. Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet, 2014, 383(9927): 1490-1502.
4. Nikolouzakis TK, Vassilopoulou L, Fragkiadaki P, et al. Improving diagnosis, prognosis and prediction by using biomarkers in CRC patients (Review). Oncol Rep, 2018, 39(6): 2455-2472.
5. Wu XX, Yue GG, Dong JR, et al. Actein inhibits tumor growth and metastasis in HER2-positive breast tumor bearing mice via suppressing AKT/mTOR and Ras/Raf/MAPK signaling pathways. Front Oncol, 2020, 10: 854.
6. Guo X, Zhou N, Chen Z, et al. Construction of ¹²⁴I-trastuzumab for noninvasive PET imaging of HER2 expression: from patient-derived xenograft models to gastric cancer patients. Gastric Cancer, 2020, 23(4): 614-626.
7. 胥润, 杜正贵. HER-2 阳性乳腺癌抗 HER-2 双靶向治疗的研究进展. 中国普外基础与临床杂志, 2021, 28(4): 544-550.
8. Siena S, Sartore-Bianchi A, Marsoni S, et al. Targeting the human epidermal growth factor receptor 2 (HER2) oncogene in colorectal cancer. Ann Oncol, 2018, 29(5): 1108-1119.
9. Tierney JF, Stewart LA, Ghersi D, et al. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials, 2007, 8: 16.
10. Seo AN, Kwak Y, Kim DW, et al. HER2 status in colorectal cancer: its clinical significance and the relationship between HER2 gene amplification and expression. PLoS One, 2014, 9(5): e98528.
11. Stahler A, Heinemann V, Neumann J, et al. Prevalence and influence on outcome of HER2/neu, HER3 and NRG1 expression in patients with metastatic colorectal cancer. Anticancer Drugs, 2017, 28(7): 717-722.
12. Meng X, Wang R, Huang Z, et al. Human epidermal growth factor receptor-2 expression in locally advanced rectal cancer: association with response to neoadjuvant therapy and prognosis. Cancer Sci, 2014, 105(7): 818-824.
13. Zhang X, Wu J, Wang L, et al. HER2 and BRAF mutation in colorectal cancer patients: a retrospective study in Eastern China. PeerJ, 2020, 8: e8602.
14. Wang XY, Zheng ZX, Sun Y, et al. Significance of HER2 protein expression and HER2 gene amplification in colorectal adenocarcinomas. World J Gastrointest Oncol, 2019, 11(4): 335-347.
15. Ingold Heppner B, Behrens HM, Balschun K, et al. HER2/neu testing in primary colorectal carcinoma. Br J Cancer, 2014, 111(10): 1977-1984.
16. Liu F, Ren C, Jin Y, et al. Assessment of two different HER2 scoring systems and clinical relevance for colorectal cancer. Virchows Arch, 2020, 476(3): 391-398.
17. Nam SK, Yun S, Koh J, et al. BRAF, PIK3CA, and HER2 oncogenic alterations according to KRAS mutation status in advanced colorectal cancers with distant metastasis. PLoS One, 2016, 11(3): e0151865.
18. Richman SD, Southward K, Chambers P, et al. HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3 256 patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials. J Pathol, 2016, 238(4): 562-570.
19. Gutierrez C, Schiff R. HER2: biology, detection, and clinical implications. Arch Pathol Lab Med, 2011, 135(1): 55-62.
20. Pyo JS, Kang G, Park K. Clinicopathological significance and diagnostic accuracy of HER2 immunohistochemistry in colorectal cancer: a meta-analysis. Int J Biol Markers, 2016, 31(4): e389-e394.
21. Bartley AN, Washington MK, Colasacco C, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: Guideline from the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J Clin Oncol, 2017, 35(4): 446-464.
22. Valtorta E, Martino C, Sartore-Bianchi A, et al. Assessment of a HER2 scoring system for colorectal cancer: results from a validation study. Mod Pathol, 2015, 28(11): 1481-1491.
23. Sartore-Bianchi A, Amatu A, Porcu L, et al. HER2 positivity predicts unresponsiveness to EGFR-targeted treatment in metastatic colorectal cancer. Oncologist, 2019, 24(10): 1395-1402.
24. Laurent-Puig P, Balogoun R, Cayre A, et al. ERBB2 alterations a new prognostic biomarker in stage Ⅲ colon cancer from a FOLFOX based adjuvant trial (PETACC8). Ann Oncol, 2016, 27(6): 149-206.
25. Sun SJ, Lin Q, Sun Q, et al. High HER-2 protein levels correlate with clinicopathological features in colorectal cancer. J Cancer Res Ther, 2016, 12(1): 323-333.
26. Wu SW, Ma CC, Li WH. Does overexpression of HER-2 correlate with clinicopathological characteristics and prognosis in colorectal cancer? Evidence from a meta-analysis. Diagn Pathol, 2015, 10: 144.
27. Li C, Liu DR, Ye LY, et al. HER-2 overexpression and survival in colorectal cancer: a meta-analysis. J Zhejiang Univ Sci B, 2014, 15(6): 582-589.
28. Marx AH, Burandt EC, Choschzick M, et al. Heterogenous high-level HER-2 amplification in a small subset of colorectal cancers. Hum Pathol, 2010, 41(11): 1577-1585.
29. Missiaglia E, Jacobs B, D’Ario G, et al. Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. Ann Oncol, 2014, 25(10): 1995-2001.
30. Siena S, Sartore-Bianchi A, Trusolino L, et al. Final results of the HERACLES trial in HER2 amplified colorectal cancer. Ann Oncol, 2016, 27(Supplement 4): iv39-iv54.
31. Wei Q, Zhang Y, Gao J, et al. Clinicopathologic characteristics of HER2-positive metastatic colorectal cancer and detection of HER2 in plasma circulating tumor DNA. Clin Colorectal Cancer, 2019, 18(3): 175-182.
32. Schuell B, Gruenberger T, Scheithauer W, et al. HER 2/neu protein expression in colorectal cancer. BMC Cancer, 2006, 6: 123.
33. Raghav K, Loree JM, Morris JS, et al. Validation of HER2 amplification as a predictive biomarker for anti–epidermal growth factor receptor antibody therapy in metastatic colorectal cancer. JCO Precision Oncology, 2019, 3(3): 1-13.
34. Dong Z, Kong L, Wan Z, et al. Somatic mutation profiling and HER2 status in KRAS-positive Chinese colorectal cancer patients. Sci Rep, 2019, 9(1): 16894.
35. Li QH, Wang YZ, Tu J, et al. Anti-EGFR therapy in metastatic colorectal cancer: mechanisms and potential regimens of drug resistance. Gastroenterol Rep (Oxf), 2020, 8(3): 179-191.
36. Meric-Bernstam F, Hurwitz H, Raghav KPS, et al. Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol, 2019, 20(4): 518-530.
37. 陈功. 2019 年结直肠癌治疗进展盘点. 肿瘤综合治疗电子杂志, 2020, 1(6): 89-90.

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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Correlation of human epidermal growth factor receptor 2 amplification with clinicopathological characteristics and prognosis of colorectal cancer patients: a meta-analysis

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