Top

Diagnostic Pathology

Published in:

Open Access 01-12-2020 | Research

HER2 expression and relevant clinicopathological features in esophageal squamous cell carcinoma in a Chinese population

Authors: Lulu Rong, Bingzhi Wang, Lei Guo, Xiuyun Liu, Bingning Wang, Jianming Ying, Liyan Xue, Ning Lu

Published in: Diagnostic Pathology | Issue 1/2020

Abstract

Background

Despite great progress in surgery and other treatments, the prognosis of patients with esophageal squamous cell carcinoma (ESCC) is still very poor. HER2 has strong therapeutic implications in certain cancers, such as breast cancer and gastric cancer. However, literature on the frequency of HER2 expression in ESCC is scarce. In the present study, HER2 protein expression, HER2 gene amplification and the relationship between HER2 status and clinicopathological characteristics were evaluated in a large cohort of Chinese ESCC patients.

Methods

A total of 857 consecutive ESCC patients who received radical esophagectomy without neoadjuvant therapy between January 2014 and October 2015 were included in this retrospective study. HER2 protein expression was analyzed by immunohistochemistry (IHC), and its correlation with clinicopathological parameters was assessed. In addition, 65 cases, including 13 HER2 overexpression (3+) cases and 52 HER2 equivocal (2+) cases from the 857-case cohort, and another 104 ESCC cases, including 1 HER2 overexpression (3+) case, 3 HER2 equivocal (2+) cases and 100 HER2 negative (1+/0) cases, were selected to construct tissue microarrays (TMAs). Dual-color in situ hybridization (DISH) was performed on the TMAs to assess HER2 gene amplification and the relationship with clinicopathological parameters.

Results

We found HER2 overexpression (3+) status in 1.5% (13/857) of cases and HER2 equivocal (2+) status in 6.1% (52/857) of cases. HER2 IHC expression was significantly associated with gender (P = 0.028). However, there were no significant correlations between HER2 IHC expression and age, tumor differentiation, pT stage, pN stage, pM stage and pTNM stage (P > 0.05). Regarding the 169 cases analyzed by DISH, 14 (of 14, 100%) HER2 overexpression (3+) cases, 10 (of 55, 18.2%) HER2 equivocal (2+) cases, and 0 (of 100, 0%) HER2 negative (1+/0) cases showed HER2 gene amplification. HER2 gene amplification was not significantly associated with clinicopathological characteristics such as age, gender, tumor differentiation, pT stage, pN stage, pM stage and pTNM stage (P > 0.05).

Conclusions

Approximately 1.5% of the Chinese ESCC patients had HER2 overexpression based on IHC. IHC and DISH had a high concordance rate. These results provide valuable insight for the future treatment of ESCC.

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108. https://doi.org/10.3322/caac.21262.CrossRefPubMed

Gonzaga IM, Soareslima SC, de Santos PT, Blanco TC, de Reis BS. Alterations in epidermal growth factor receptors 1 and 2 in esophageal squamous cell carcinomas. BMC Cancer. 2012;12:569. https://doi.org/10.1186/1471-2407-12-569.CrossRefPubMedPubMedCentral

Fichter CD, Gudernatsch V, Przypadlo CM, Follo M, Schmidt G, Werner M, et al. ErbB targeting inhibitors repress cell migration of esophageal squamous cell carcinoma and adenocarcinoma cells by distinct signaling pathways. J Mol Med (Berl). 2014;92:1209–23. https://doi.org/10.1007/s00109-014-1187-5.CrossRef

Shan L, Ying J, Lu N. HER2 expression and relevant clinicopathological features in gastric and gastroesophageal junction adenocarcinoma in a Chinese population. Diagn Pathol. 2013;8:76. https://doi.org/10.1186/1746-1596-8-76.CrossRefPubMedPubMedCentral

Zhan N, Dong W, Tang Y, Wang Z, Xiong C. Analysis of HER2 gene amplification and protein expression in esophageal squamous cell carcinoma. Med Oncol. 2012;29:933–40. https://doi.org/10.1007/s12032-011-9850-y.CrossRefPubMed

Mimura K, Kono K, Hanawa M, Mitsui F, Sugai H, Miyagawa N, et al. Frequencies of HER-2/neu expression and gene amplification in patients with oesophageal squamous cell carcinoma. Br J Cancer. 2005;92:1253–60. https://doi.org/10.1038/sj.bjc.6602499.CrossRefPubMedPubMedCentral

Sato-Kuwabara Y, Neves JI, Fregnani JH, Sallum RA, Soares FA. Evaluation of gene amplification and protein expression of HER-2/neu in esophageal squamous cell carcinoma using fluorescence in situ hybridization (FISH) and immunohistochemistry. BMC Cancer. 2009;9:6. https://doi.org/10.1186/1471-2407-9-6.CrossRefPubMedPubMedCentral

Rice TW, Gress DM, Patil DT, Hofstetter WL, Kelsen DP, Blackstone EH. Cancer of the esophagus and esophagogastric junction-major changes in the American joint committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67:304–17. https://doi.org/10.3322/caac.21399.CrossRefPubMed

Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, 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. J Clin Oncol. 2013;31:3997–4013. https://doi.org/10.1200/JCO.2013.50.9984.CrossRefPubMed

10.

Dreilich M, Wanders A, Brattstrom D, Bergstrom S, Hesselius P, Wagenius G, et al. HER-2 overexpression (3+) in patients with squamous cell esophageal carcinoma correlates with poorer survival. Dis Esophagus. 2006;19:224–31. https://doi.org/10.1111/j.1442-2050.2006.00570.x.CrossRefPubMed

11.

Nig AMK, Reeh M, Dancau A, Rathjens M, Gros S. Concordance of HER2 status in primary tumour and lymph node metastases in patients with esophageal carcinoma. Anticancer Res. 2013;33:4975–82.

12.

Kawaguchi Y, Kono K, Mimura K, Mitsui F, Sugai H, Akaike H, et al. Targeting EGFR and HER-2 with cetuximab- and trastuzumab-mediated immunotherapy in oesophageal squamous cell carcinoma. Br J Cancer. 2007;97:494–501. https://doi.org/10.1038/sj.bjc.6603885.CrossRefPubMedPubMedCentral

13.

Schoppmann SF, Jesch B, Friedrich J, Wrba F, Schultheis A, Pluschnig U, et al. Expression of her-2 in carcinomas of the esophagus. Am J Surg Pathol. 2010;34:1868–73. https://doi.org/10.1097/PAS.0b013e3181f8be17.CrossRefPubMed

14.

Gibault L, Metges JP, Conan-Charlet V, Lozac'H P, Robaszkiewicz M, Bessaguet C, et al. Diffuse EGFR staining is associated with reduced overall survival in locally advanced oesophageal squamous cell cancer. Br J Cancer. 2005;93:107–15. https://doi.org/10.1038/sj.bjc.6602625.CrossRefPubMedPubMedCentral

15.

Hatogai K, Fujii S, Kojima T, Daiko H, Nomura S, Doi T, et al. Large-scale comprehensive immunohistochemical biomarker analyses in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol. 2017;143:2351–61. https://doi.org/10.1007/s00432-017-2482-7.CrossRefPubMed

16.

Shibata-Kobayashi S, Yamashita H, Okuma K, Shiraishi K, Igaki H, Ohtomo K, et al. Correlation among 16 biological factors [p53, p21(waf1), MIB-1 (Ki-67), p16(INK4A), cyclin D1, E-cadherin, Bcl-2, TNF-alpha, NF-kappaB, TGF-beta, MMP-7, COX-2, EGFR, HER2/neu, ER, and HIF-1alpha] and clinical outcomes following curative chemoradiation therapy in 10 patients with esophageal squamous cell carcinoma. Oncol Lett. 2013;5:903–10. https://doi.org/10.3892/ol.2013.1130.CrossRefPubMedPubMedCentral

17.

Akamatsu M, Matsumoto T, Oka K, Yamasaki S, Sonoue H, Kajiyama Y, et al. c-erbB-2 oncoprotein expression related to chemoradioresistance in esophageal squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2003;57:1323–7. https://doi.org/10.1016/s0360-3016(03)00782-x.CrossRefPubMed

18.

Bartley AN, Washington MK, Colasacco C, Ventura CB, Ismaila N, Benson AR, 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;35:446–64. https://doi.org/10.1200/JCO.2016.69.4836.CrossRefPubMed

19.

Chen Y, Zhu S, Xu X, Zhao AN, Hu J. Expression levels of HER2 and MRP1 are not prognostic factors of long-term survival in 829 patients with esophageal squamous cell carcinoma. Oncol Lett. 2016;11:745–52. https://doi.org/10.3892/ol.2015.3975.CrossRefPubMed

20.

Fazlollahi L, Remotti HE, Iuga A, Yang HM, Lagana SM, Sepulveda AR. HER2 heterogeneity in Gastroesophageal Cancer detected by testing biopsy and resection specimens. Arch Pathol Lab Med. 2018;142:516–22. https://doi.org/10.5858/arpa.2017-0039-OA.CrossRefPubMed

21.

Sunpaweravong P, Sunpaweravong S, Puttawibul P, Mitarnun W, Zeng C, Baron AE, et al. Epidermal growth factor receptor and cyclin D1 are independently amplified and overexpressed in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol. 2005;131:111–9. https://doi.org/10.1007/s00432-004-0610-7.CrossRefPubMed

22.

Horii R, Matsuura M, Iwase T, Ito Y, Akiyama F. Comparison of dual-color in-situ hybridization and fluorescence in-situ hybridization in HER2 gene amplification in breast cancer. Breast Cancer. 2014;21:598–604. https://doi.org/10.1007/s12282-012-0436-0.CrossRefPubMed

23.

Fusco N, Bosari S. HER2 aberrations and heterogeneity in cancers of the digestive system: implications for pathologists and gastroenterologists. World J Gastroenterol. 2016;22:7926–37. https://doi.org/10.3748/wjg.v22.i35.7926.CrossRefPubMedPubMedCentral

24.

Krishnamurti U, Silverman JF. HER2 in breast cancer: a review and update. Adv Anat Pathol. 2014;21:100–7. https://doi.org/10.1097/PAP.0000000000000015.CrossRefPubMed

25.

Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS, et al. Human epidermal growth factor receptor 2 testing in breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol. 2018;36:2105–22. https://doi.org/10.1200/JCO.2018.77.8738.CrossRefPubMed

26.

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. https://doi.org/10.1016/S0140-6736(10)61121-X.CrossRefPubMed

27.

Kasper S, Schuler M. Targeted therapies in gastroesophageal cancer. Eur J Cancer. 2014;50:1247–58. https://doi.org/10.1016/j.ejca.2014.01.009.CrossRefPubMed

28.

Mimura K, Izawa S, Siba S, Maruyama T, Watanabe M, Kawaguchi Y, et al. The effect of immune-based therapy with cytotoxic T lymphocyte and molecular targeting therapy for HER2 in esophageal squamous cell carcinoma. Gan To Kagaku Ryoho. 2011;38:1918–20.PubMed

29.

Zhang L, Ma J, Han Y, Liu J, Zhou W, Hong L, et al. Targeted therapy in esophageal cancer. Expert Rev Gastroenterol Hepatol. 2016;10:595–604. https://doi.org/10.1586/17474124.2016.1140036.CrossRefPubMed

Title: HER2 expression and relevant clinicopathological features in esophageal squamous cell carcinoma in a Chinese population
Authors: Lulu Rong
Bingzhi Wang
Lei Guo
Xiuyun Liu
Bingning Wang
Jianming Ying
Liyan Xue
Ning Lu
Publication date: 01-12-2020
Publisher: BioMed Central
Published in: Diagnostic Pathology / Issue 1/2020
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/s13000-020-00950-y

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

HER2 expression and relevant clinicopathological features in esophageal squamous cell carcinoma in a Chinese population

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2020

Clinicopathological and immunohistochemical study of 29 cases of solid-pseudopapillary neoplasms of the pancreas in patients under 20 years of age along with detailed review of literature

Ovarian mesonephric-like adenocarcinoma arising in serous borderline tumor: a case report with complex morphological and molecular analysis

ROC-1, P21 and CAIX as markers of tumor aggressiveness in bladder carcinoma in Egyptian patients

Endoscopic and clinicopathological characteristics of colorectal T/NK cell lymphoma

A combination of cytokeratin 5/6, p63, p40 and MUC5AC are useful for distinguishing squamous cell carcinoma from adenocarcinoma of the cervix

Next generation sequencing to decipher concurrent loss of PMS2 and MSH6 in colorectal cancer