Clinicopathological Significance Of Human Epidermal Growth Factor Receptor- 2 (HER-2/Neu) Over-Expression In Gastric And Oesophageal Carcinomas Of Upper Gastrointestinal Biopsies
Keywords:
Adenocarcinoma, endoscopic biopsy, HER-2/neu, immunohistochemistry.
Abstract
INTRODUCTION: HER-2/neu plays a key role in the pathogenesis of gastric and oesophageal carcinomas and it’s over expression has been documented in 6.8–34% of gastric carcinomas and 10-12.1% of oesophageal adenocarcinoma. Detecting the HER-2/neu status is a prerequisite for monoclonal antibody therapy. In this study, immunohistochemistry was used to detect HER-2/neu over- expression in gastric and oesophageal carcinomas. OBJECTIVE: To associate HER-2/neu over-expression with age, sex, type and grade of gastric and esophageal carcinomas in upper gastrointestinal (UGI) endoscopic biopsies. METHODS: HER-2/neu expression was investigated by immunohistochemistry on esophageal and gastric carcinomas of UGI endoscopic biopsies received at our institution. Association between the expression of HER-2/neu and clinico-pathological parameters was statistically analysed. RESULTS: The association was not statistically significant between age, sex and grade of the tumour with HER-2/neu overexpression. HER-2/neu overexpression was seen in 14.2% of gastric adenocarcinomas, 20% of esophageal adenocarcinomas and 4% of esophageal squamous cell carcinomas. Predominantly, intestinal type (9.5%) of gastric carcinoma showed HER-2neu over-expression followed by diffuse type (2.3%) and mixed type (2.3%). CONCLUSION: In view of increasing trend of UGI tract malignancies and associated poor survival of advanced carcinomas, assessing HER-2/neu over-expression in gastric and esophageal carcinomas is helpful to decide the utility of adjuvant targeted chemotherapy.References
1. Yan SY, Hu Y, Fan JG, Tao GQ, Lu YM, Cai X et al. Clinicopathologic significance of HER-2/neu protein expression and gene amplification in gastric carcinoma. World Journal of Gastroenterology 2011;17:1501-6.
2. Gowryshankar A, Nagaraja V, Eslick G.D. HER2 status in Barrett’s esophagus & esophageal cancer: A meta-analysis. Journal of Gastrointestinal Oncology 2014;5:25-35.
3. Amin A, Gilmour H, Graham L,Brown P, Terrace J, Crofts T.J. Gastric adenocarcinoma missed at endoscopy. J R Coll Surg Edinb 2002;47:681-4.
4. Lee S, Boer WB, Fermoyle S et al. Human epidermal growth factor receptor 2 testing in gastric carcinoma: Issues related to heterogeneity in biopsies and resections. Histopathology 2011;59:832-40.
5. Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer: Results from a validation study. Histopathology 2008;52:797-805.
6. Qiu M, Zhou Y, Zhang X, Wang Z, Wang F, Shao J et al. Lauren classification combined with HER2 status is a better prognostic factor in Chinese gastric cancer patients. BMC Cancer 2014;14:823.
7. Ahmadi L, Kamkari S, Mokarram P.HER-2/neu and E-cadherin Expression and Microsatellite Instability in Gastric Dysplasia. Middle East Journal of Digestive Diseases 2011;3:20-7.
8. Jawalkar S, Arakeri S. Role of endoscopic biopsies in upper gastrointestinal diseases. Research Journal of Pharmaceutical, Biological and Chemical Sciences 2015;6: 977-83.
9. Rashmi K, Horakerappa MS, Karar A, Mangala G. International Journal of Medical Research & Health Sciences 2013;2:418-24.
10. Silva JDB, Leitao D, Afonso L et al. Association of ERBB2 gene status with Histopathological parameters and disease-specific survival in gastric carcinoma patients. B J Cancer 2009;00:487-93.
11. Moelans CB, Diest PJ, Milne ANA, et al. HER-2/neu Testing and Therapy in Gastroesophageal Adenocarcinoma. Pathology Research International 2011;ID 674182
12. Ruschoff J, Dietel M, Kreipe H. HER2 diagnostics in gastric cancer—guideline validation and development of standardized immunohistochemical testing. Virchows Arch.2010;457:299-307.
13. Junco JM, Jane H, Sawyer M B. Overview of Trastuzumab’s Utility for Overview Adenocarcinoma: emerging therapeutic options and diagnostic challenges. Connection 2010;15:47-51.
14. Schoppmann SF, Jesch B, Friedrich J et al. Expression of HER-2 in Carcinomas of the Esophagus. Am J SurgPathol 2010;34:1868-73.
15. Grabsch H, Sivkumar S, Gray S et al. HER2 expression in Gastric Cancer: Rare, heterogenous and of no prognostic value- conclusion from 924 cases of two independent series. Cell Oncol 2010;32:57-65.
16. European Medicines Agency. Assessment Report for Herceptin. Doc. Ref. No. EMA/842364/2009.
17. Bang YJ, Van CE, Feyereislova A, at al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER-2/neu positive advanced gastric or gastroesophageal junction cancer (ToGA): A phase 3, open label, randomized control trial. Lancet 2010;376:687-97.
18. Reichelt U, Duesedau P, Tsourlakis MC et al. Frequent homogenous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus. Modern Pathology 2007;20:120-9.
19. Schoppmann SF, Jesh B, Zacheri J et al. HER-2 status in primary oesophageal cancer, lymph nodes and distant metastases. British Journal of Surgery 2011;98:1408-13.
20. Allgayer H, Babic R, Gruetzner KU et al. C-erb-2 is of independent prognostic relevance in gastric cancer and is associated with the expressison of tumor associated protease systems. J Clin Oncol 2000;18:2201-9.
21. Gravlos C, Jimeno A. HER2 in gastric cancer: A new prognostic factor and a novel therapeutic target. Annals of oncology 2008;19:1523-9.
22. Marx AH, Tharun L, Muth J et al. HER-2 amplification is highly homogenous in gastric cancer. Human Pathology 2009;40:769-77.
23. Tanner M, Hollmen M, Junttila TT et al. Amplification of HER-2 in gastric carcinoma: Association with Topoisomerase II 1α gene amplification, intestinal type, poor prognosis and sensitivity to Trastuzumab. Annals of Oncology 2005;16:273-8.
24. Principles, Pitfalls and Standardization. In: Zorab R. (Eds). Diagnostic Immunohistochemistry. 1st ed. Philadelphia: Chruchill Livingstone;2002. p.3-43.
25. Dreilich M, Wangers A, Brattstrom D et al. Her-2 overexpression (3+) in patients with squamous cell carcinoma correlates with poor survival. Disorders of the Esophagus 2006;19:224-31.
26. Akamatsu M, Matsumoto T, Oka K et al. c-erb B-2 oncoprotein expression related to chemoradioresistance in esophageal squamous cell carcinoma. Int J Radiot Oncol Bio Phys 2003;57:1323-7.
27. Zhou Z, Hick DG. Oncogene and Cancer- From Bench to Clinic [internet].USA: 2013. HER2 Amplification or Overexpression in Upper GI Tract and Breast Cancer with Clinical Diagnosis and Treatment.[cited 2017 March 24]. Available from: http://dx.doi.org/10.5772/53921
28. Wang S, Zheng G, Chen L et al. Effect of HER-2/neu expression on prognosis of gastric cancer: A Meta-analysis. Asian Pacific J Cancer Preview 2011;12:1417- 23.
29. Hu Y, Bandla S, Godfrey TE, et al. HER2 amplification, overexpression and score criteria in esophageal adenocarcinoma. Modern Pathology 2011;24:899-907.
2. Gowryshankar A, Nagaraja V, Eslick G.D. HER2 status in Barrett’s esophagus & esophageal cancer: A meta-analysis. Journal of Gastrointestinal Oncology 2014;5:25-35.
3. Amin A, Gilmour H, Graham L,Brown P, Terrace J, Crofts T.J. Gastric adenocarcinoma missed at endoscopy. J R Coll Surg Edinb 2002;47:681-4.
4. Lee S, Boer WB, Fermoyle S et al. Human epidermal growth factor receptor 2 testing in gastric carcinoma: Issues related to heterogeneity in biopsies and resections. Histopathology 2011;59:832-40.
5. Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer: Results from a validation study. Histopathology 2008;52:797-805.
6. Qiu M, Zhou Y, Zhang X, Wang Z, Wang F, Shao J et al. Lauren classification combined with HER2 status is a better prognostic factor in Chinese gastric cancer patients. BMC Cancer 2014;14:823.
7. Ahmadi L, Kamkari S, Mokarram P.HER-2/neu and E-cadherin Expression and Microsatellite Instability in Gastric Dysplasia. Middle East Journal of Digestive Diseases 2011;3:20-7.
8. Jawalkar S, Arakeri S. Role of endoscopic biopsies in upper gastrointestinal diseases. Research Journal of Pharmaceutical, Biological and Chemical Sciences 2015;6: 977-83.
9. Rashmi K, Horakerappa MS, Karar A, Mangala G. International Journal of Medical Research & Health Sciences 2013;2:418-24.
10. Silva JDB, Leitao D, Afonso L et al. Association of ERBB2 gene status with Histopathological parameters and disease-specific survival in gastric carcinoma patients. B J Cancer 2009;00:487-93.
11. Moelans CB, Diest PJ, Milne ANA, et al. HER-2/neu Testing and Therapy in Gastroesophageal Adenocarcinoma. Pathology Research International 2011;ID 674182
12. Ruschoff J, Dietel M, Kreipe H. HER2 diagnostics in gastric cancer—guideline validation and development of standardized immunohistochemical testing. Virchows Arch.2010;457:299-307.
13. Junco JM, Jane H, Sawyer M B. Overview of Trastuzumab’s Utility for Overview Adenocarcinoma: emerging therapeutic options and diagnostic challenges. Connection 2010;15:47-51.
14. Schoppmann SF, Jesch B, Friedrich J et al. Expression of HER-2 in Carcinomas of the Esophagus. Am J SurgPathol 2010;34:1868-73.
15. Grabsch H, Sivkumar S, Gray S et al. HER2 expression in Gastric Cancer: Rare, heterogenous and of no prognostic value- conclusion from 924 cases of two independent series. Cell Oncol 2010;32:57-65.
16. European Medicines Agency. Assessment Report for Herceptin. Doc. Ref. No. EMA/842364/2009.
17. Bang YJ, Van CE, Feyereislova A, at al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER-2/neu positive advanced gastric or gastroesophageal junction cancer (ToGA): A phase 3, open label, randomized control trial. Lancet 2010;376:687-97.
18. Reichelt U, Duesedau P, Tsourlakis MC et al. Frequent homogenous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus. Modern Pathology 2007;20:120-9.
19. Schoppmann SF, Jesh B, Zacheri J et al. HER-2 status in primary oesophageal cancer, lymph nodes and distant metastases. British Journal of Surgery 2011;98:1408-13.
20. Allgayer H, Babic R, Gruetzner KU et al. C-erb-2 is of independent prognostic relevance in gastric cancer and is associated with the expressison of tumor associated protease systems. J Clin Oncol 2000;18:2201-9.
21. Gravlos C, Jimeno A. HER2 in gastric cancer: A new prognostic factor and a novel therapeutic target. Annals of oncology 2008;19:1523-9.
22. Marx AH, Tharun L, Muth J et al. HER-2 amplification is highly homogenous in gastric cancer. Human Pathology 2009;40:769-77.
23. Tanner M, Hollmen M, Junttila TT et al. Amplification of HER-2 in gastric carcinoma: Association with Topoisomerase II 1α gene amplification, intestinal type, poor prognosis and sensitivity to Trastuzumab. Annals of Oncology 2005;16:273-8.
24. Principles, Pitfalls and Standardization. In: Zorab R. (Eds). Diagnostic Immunohistochemistry. 1st ed. Philadelphia: Chruchill Livingstone;2002. p.3-43.
25. Dreilich M, Wangers A, Brattstrom D et al. Her-2 overexpression (3+) in patients with squamous cell carcinoma correlates with poor survival. Disorders of the Esophagus 2006;19:224-31.
26. Akamatsu M, Matsumoto T, Oka K et al. c-erb B-2 oncoprotein expression related to chemoradioresistance in esophageal squamous cell carcinoma. Int J Radiot Oncol Bio Phys 2003;57:1323-7.
27. Zhou Z, Hick DG. Oncogene and Cancer- From Bench to Clinic [internet].USA: 2013. HER2 Amplification or Overexpression in Upper GI Tract and Breast Cancer with Clinical Diagnosis and Treatment.[cited 2017 March 24]. Available from: http://dx.doi.org/10.5772/53921
28. Wang S, Zheng G, Chen L et al. Effect of HER-2/neu expression on prognosis of gastric cancer: A Meta-analysis. Asian Pacific J Cancer Preview 2011;12:1417- 23.
29. Hu Y, Bandla S, Godfrey TE, et al. HER2 amplification, overexpression and score criteria in esophageal adenocarcinoma. Modern Pathology 2011;24:899-907.
Published
2018-11-30
Issue
Section
Original Article
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access at http://opcit.eprints.org/oacitation-biblio.html).
