Estimation of Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Colorectal Adenocarcinoma for HER2 Targeted Therapy
DOI:
https://doi.org/10.52206/jsmc.2024.14.4.868Abstract
Background: Colorectal carcinoma (CRC) ranks among the top cancers globally, with high mortality rates despite treatment advancements. Emerging therapeutic targets, including HER2, well-studied in breast and gastric cancers, are less explored in CRC literature.
Objectives: To determine the frequency of HER2 expression in colorectal adenocarcinoma for HER2-targeted therapy and its association with various clinic-pathological variables.
Materials and Methods: This cross-sectional study was conducted at the Department of Histopathology, Rehman Medical Institute (RMI), Peshawar, from November 15, 2022, to April 30, 2023. A total of 110 cases were included through consecutive sampling. The study included patients of both genders and all age groups who had undergone colectomy (right or left hemicolectomy, extended right hemicolectomy, abdominoperineal resection) and were previously diagnosed with CRC based on colonoscopic biopsies. Colonoscopic biopsy specimens and patients who had undergone neoadjuvant therapy were excluded. Immunohistochemistry assay for HER2 was performed, and the results were interpreted.
Results: The mean age (SD) of study sample was 45 (6.12) years. There was a predominance of male patients. Out of the total 110 patients, HER2 expression was positive in 69 (62.73%) and negative in 41 (37.27%) patients. The lesions were predominantly located in the rectum and left colon in 77 (70.00%) of the patients. Histologically, 92 (83.64%) patients had non-mucinous tumor variants. Among the 69 positive cases, 32 (29.09%) were scored as 1+, 24 (21.82%) as 2+, and 13 (11.82%) as 3+. Tumor grade, tumor stage, HER2 expression, and score were statistically significantly associated with IHC staining intensity (p < 0.001). Similarly, tumor grade, tumor stage, and HER2 score were statistically significantly associated with positivity status (p < 0.001). Furthermore, statistically significant relationship between the degree of differentiation (tumor grade), tumor stage, IHC staining intensity and the score of HER2 overexpression was observed (p < 0.001).
Conclusion: In our study, HER2 expression was observed in a significant number of patients. The findings indicate that HER2 expression correlates with specific tumor characteristics suggesting its potential as a biomarker in management for this disease. Further research with larger sample sizes and broader geographical diversity is recommended to better understand HER2's biological role in cancer.
Keywords: Colorectal adenocarcinoma, Gastrointestinal system, HER2, Immunohistochemistry, Targeted therapy.
References
Sung H, Ferlay J, Siegel RL. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2021;71(3):209-249.DOI: https://doi.org/10.3322/caac.21660
Ramsoekh D, Van Leerdam M, Van Ballegooijen M. Population screening for colorectal cancer: faeces, endoscopes or X-rays? Analytical Cellular Pathology. 2007;29(3):185-194. DOI: https://doi.org/10.1155/2007/610496
Gene symbol reports 2024.
Shabbir A, Mirza T, Khalid AB. Frequency of Her2/neu expression in colorectal adenocarcinoma: a study from developing South Asian Country. BMC Cancer. 2016;16(1):855. DOI: https://doi.org/10.1186/s12885-016-2912-y
Hanif M, Zaidi P, Kamal S. Institution-based cancer incidence in a local population in Pakistan: nine year data analysis. Asian Pac J Cancer Prev. 2009;10(2):227-230
Andersen TI, Paus E, Nesland JM. Detection of C-ERBB-2 related protein in sera from breast cancer patients relationship to ERBB2 gene amplification and c-erbB-2 protein overexpression in tumour. Acta Oncologica. 1995;34(4):499-504. DOI: https://doi.org/10.3109/02841869509094014
Porêbska IHar³oziñska A, Bojarowski T. Expression of the tyrosine kinase activity growth factor receptors (EGFR, ERB B2, ERB B3) in colorectal adenocarcinomas and adenomas. Tumor biology. 2000;21(2):105-115. DOI: https://doi.org/10.1159/000030116
Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2000;103(2):211-225. DOI: https://doi.org/10.1016/s0092-8674(00)00114-8
Rusch V, Baselga J, Cordon-Cardo C. Differential expression of the epidermal growth factor receptor and its ligands in primary non-small cell lung cancers and adjacent benign lung. Cancer research. 1993;53(10):2379-2385
Ross JS, McKenna Bj. The HER-2/neu oncogene in tumors of the gastrointestinal tract. Cancer investigation. 2001;19(5):554-568. DOI: https://doi.org/10.1081/cnv-100103852
Farzand S, Siddique T, Saba K. Frequency of HER2/neu overexpression in adenocarcinoma of the gastrointestinal system. World J Gastroenterol. 2014;20(19):5889-5896. DOI: https://doi.org/10.3748/wjg.v20.i19.5889
Xi Y, Xu P. Global colorectal cancer burden in 2020 and projections to 2040. Translational oncology. 2021;14(10):101-174. DOI: https://doi.org/10.1016/j.tranon.2021.101174
Iqbal N, Iqbal N. Human epidermal growth factor receptor 2 (HER2) in cancers: overexpression and therapeutic implications. Molecular biology international. 2014;2014(1):8527-48. DOI: https://doi.org/10.1155/2014/852748
Hortobagyi GN. Overview of treatment results with trastuzumab (Herceptin) in metastatic breast cancer. Seminars in oncology; 2001: Elsevier.
Bang Y-J, Van Cutsem E, Feyereislova A. 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. The Lancet. 2010;376(9742):687-697. DOI: https://doi.org/10.1016/S0140-6736(10)61121-X
Elias D, Glehen O, Pocard M. A comparative study of complete cytoreductive surgery plus intraperitoneal chemotherapy to treat peritoneal dissemination from colon, rectum, small bowel, and nonpseudomyxoma appendix. Annals of surgery. 2010;251(5):896-901. DOI: https://doi.org/10.1097/SLA.0b013e3181d9765d
Talsma K, van Hagen P, Grotenhuis BA. Comparison of the 6th and 7th Editions of the UICC-AJCC TNM Classification for Esophageal Cancer. Annals of surgical oncology. 2012;19:2142-2148. DOI: https://doi.org/10.1245/s10434-012-2218-5
Rosai J. Rosai and Ackerman's surgical pathology e-book: Elsevier Health Sciences; 2011.
Edition SEdge S, Byrd D. AJCC cancer staging manual. AJCC cancer staging manual. 2017
Cenaj O, Ligon AH, Hornick JL. Detection of ERBB2 amplification by next-generation sequencing predicts HER2 expression in colorectal carcinoma. American journal of clinical pathology. 2019;152(1):97-108. DOI: https://doi.org/10.1093/ajcp/aqz031
Ross JS, Fakih M, Ali SM. Targeting HER2 in colorectal cancer: The landscape of amplification and short variant mutations in ERBB2 and ERBB3. Cancer. 2018;124(7):1358-1373. DOI: https://doi.org/10.1002/cncr.31125
Kamal LA, Jalal JA. Immunohistochemical expression of HER2/neu in colorectal carcinoma in Erbil city, Kurdistan Region. Zanco Journal of Medical Sciences (Zanco J Med Sci). 2019;23(3):421-428
Sayadnejad N, Firouzjahi A, Shafaee S. Immunohistochemical study of HER2/neu expression in colorectal cancer and its relation to other clinicopathological criteria and prognostic factors. Int J Cancer Manag. 2017;10(5):e5700. DOI: https://doi.org/10.5812/ijcm.5700
Elwy DA, Adelaziz A, El-sheikh SA. Immunohistochemical expression of HER2/neu in colorectal carcinoma. Med J Cairo Univ. 2012;80(2):467-477
McKay JA, Loane JF, Ross VG. c-erbB-2 is not a major factor in the development of colorectal cancer. Br J Cancer. 2002;86(4):568-573. DOI: https://doi.org/10.1038/sj.bjc.6600127
Wu QB, Sun GP. Expression of COX-2 and HER-2 in colorectal cancer and their correlation. World J Gastroenterol. 2015;21(20):6206-6214. DOI: https://doi.org/10.3748/wjg.v21.i20.6206
Additional Files
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 The authors retain the copyrights. Authors are permitted and encouraged to post their work online (e.g. in institutional repositories or on their website), as it can lead to productive exchanges, as well as greater citation of published work.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Readers may “Share-copy and redistribute the material in any medium or format” and “Adapt-remix, transform, and build upon the material”. The readers must give appropriate credit to the source of the material and indicate if changes were made to the material. Readers may not use the material for commercial purpose. The readers may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.