Evaluation of Her2 Positivity in Gastric Cancer Using Two Different Methods: A Prospective Study
Year 2025,
Volume: 35 Issue: 1, 21 - 30, 28.02.2025
Abdi İbrahim Sönmez
,
Alper Sevinc
,
İbrahim Sarı
,
İrfan Koruk
Musa Aydınlı
Serdar Öztuzcu
,
Beyhan Cengiz
Abstract
ABSTRACT
BACKGROUND: Stomach cancer is one of the most common gastrointestinal tract tumors. Its incidence varies according to ethnic group, geographical conditions, dietary habits, economic status, lifestyle and Helicobacter pylori prevalence. Genetic factors play a major role in the pathogenesis of gastric cancer, and the human epidermal growth factor receptor 2 Her2/neu (c-erb B2) gene is one of these factors.
METHOD: The objective of this study is to compare any correlation between the amplification level of Her2/neu gene in gastric cancer by real-time polymerase chain reaction (RT-PCR) with Her2 protein overexpression obtained from the same tissue and studied with immunohistochemisry (IHC), and in the event of positivity, to determine its relationshipwith other known prognostic factors such as age, gender, stage, tumor localization and histological type.
RESULTS: IHC results indicated Her2 overexpression in 5 (10%) patients and RT-PCRindicated amplification also in 5 (10%) patients. There was no significant correlation between the results determined by the two methods (p> 0.05). Additionally, no statistically significant difference was detected between prognostic factors and gene expressions in tumor tissues (p> 0.05).
CONCLUSION: Her2 gene amplification and protein overexpression can potentially contribute to tumor development. Further studies are needed to evaluate false negativity, investigate patient survival in terms of its contribution to prognosis, and corroborate our hypothesis.
Supporting Institution
yok
Thanks
We thank Esma Özkara from biology department for all help in our study.
References
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- 27. Rüschoff J, Nagelmeier I, Baretton G, Dietel M, Höfler H, Schildhaus HU et al. Her2-Diagnostik beim Magenkarzinom. Was ist anders im Vergleich zum Mammakarzinom? [Her2 testing in gastric cancer. What is different in comparison to breast cancer?]. Pathologe. 2010 May;31(3):208-17. German.
- 28. Wang HB, Liao XF, Zhang J. Clinicopathological factors associated with HER2-positive gastric cancer: A meta-analysis. Medicine (Baltimore). 2017 Nov;96(44):e8437.
- 29. Senel F. Clinicopathologic significance of human epidermal growth factor receptor 2 expression and gene amplification in gastric carcinoma. J Cancer Res Ther. 2022 Dec;18(Supplement):S299-S304
- 30. Baykara M, Benekli M, Ekinci O, Irkkan SC, Karaca H, Demirci U et al. Anatolian Society of Medical Oncology (ASMO). Clinical significance of HER2 overexpression in gastric and gastroesophageal junction cancers. J Gastrointest Surg. 2015 Sep;19(9):1565-71.
- 31. Uprak TK, Attaallah W, Çelikel ÇA, Ayrancı G, Yeğen C. HER-2 incidence in gastric cancer, its association with prognosis and clinicopathological parameters. J of National Surg. 2015 Aug 18;31(4):207-13.
- 32. 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: 2845-2856.
- 33. Gurbuz M, Doğan İ, Akkuş E, Karadag I, Karakaya S, Erol C et al. Clinicopathological Factors concerning HER2 Status in Metastatic Gastric Cancer: A Retrospective Observational Study Journal of oncological sciences 2022 8(1);14-19
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- 35. Giuffrè G, Ieni A, Barresi V, Caruso RA, Tuccari G. HER2 status in unusual histological variants of gastric adenocarcinomas. J Clin Pathol 2012;65: 237-241.
- 36. Risio M, De Rosa G, Sarotto I, Casorzo L, Capussotti L, Torchio B et al. HER2 testing in gastric cancer: molecular morphology and storage time-related changes in archival samples. Int J Oncol. 2003 Nov;23(5):1381-7. PMID: 14532980.
- 37. Königshoff M, Wilhelm J, Bohle RM, Pingoud A, Hahn M. HER-2/neu gene copy number quantified by real-time PCR: comparison of gene amplification, heterozygosity, and immunohistochemical status in breast cancer tissue. Clin Chem. 2003 Feb;49(2):219-29.
- 38. Dabbs DJ, Klein ME, Mohsin SK, Tubss RR, Shuai Y, Bhargava R. High false-negative rate of HER2 quantitative reverse transcription polymerase chain reaction of the Oncotype DX test: An independent quality assurance study. J Clin Oncol 2011;29(32): 4279-4285.
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- 40. Kameda T, Yasui W, Yoshida K, Tsujino T, Nakayama H, Ito M et al. Expression of ERBB2 in human gastric carcinomas: the relationship between p185ERBB2 expression and the gene amplification. Cancer Res. 1990 Dec 15;50(24):8002-9. PMID: 1979253.
- 41. O'Malley FP, Parkes R, Latta E, Tjan S, Zadro T, Mueller R, et al. Comparison of HER2/neu status assessed by quantitative polymerase chain reaction and immunohistochemistry. Am J Clin Pathol. 2001 Apr;115(4):504-11.
- 42. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al; ToGA Trial Investigators. 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, randomized controlled trial. Lancet. 2010 Aug 28;376(9742):687-97.
Year 2025,
Volume: 35 Issue: 1, 21 - 30, 28.02.2025
Abdi İbrahim Sönmez
,
Alper Sevinc
,
İbrahim Sarı
,
İrfan Koruk
Musa Aydınlı
Serdar Öztuzcu
,
Beyhan Cengiz
References
- 1. Machlowska J, Baj J, Sitarz M, Maciejewski R, Sitarz R. Gastric Cancer: Epidemiology, Risk Factors, Classification, Genomic Characteristics and Treatment Strategies. Int J Mol Sci. 2020 Jun 4;21(11):4012.
- 2. Gravalos C, Jimeno A. Her2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol. 2008;19(9): 1523-1529.
- 3. Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. Lancet. 2020 Aug 29;396(10251):635-648.
- 4. Yang WJ, Zhao HP, Yu Y, Wang JH, Guo L, Liu JY, et al. Updates on global epidemiology, risk, and prognostic factors of gastric cancer. World J Gastroenterol. 2023 Apr 28;29(16):2452-2468.
- 5. Nemtsova MV, Kuznetsova EB, Bure IV. Chromosomal Instability in Gastric Cancer: Role in Tumor Development, Progression, and Therapy. Int J Mol Sci. 2023 Nov 30;24(23):16961.
- 6. Christodoulidis G, Koumarelas KE, Kouliou MN, Thodou E, Samara M. Gastric Cancer in the Era of Epigenetics. Int J Mol Sci. 2024 Mar 16;25(6):3381.
- 7. Friedlaender A, Subbiah V, Russo A, Banna GL, Malapelle U, Rolfo C et al. EGFR and HER2 exon 20 insertions in solid tumors: from biology to treatment. Nat Rev Clin Oncol. 2022 Jan;19(1):51-69.
- 8. Valenza C, Guidi L, Battaiotto E, Trapani D, Sartore Bianchi A, Siena S et al. Targeting HER2 heterogeneity in breast and gastrointestinal cancers. Trends Cancer. 2024 Feb;10(2):113-123.
- 9. Okines AF, Cunningham D. Transtuzumab in gastric cancer. Eur J Cancer 2010;46(11): 1949-1959.
- 10. Kang Y, Bang Y, Lordick F, Park SR, Sawaki A, Chung HC, et al. Incidence of gastric and gastro-esophageal cancer in the ToGA trial: correlation with HER2 positivity 2008 Gastrointestinal Cancers Symposium. 75 (Abstr 11).
- 11. Guan WL, He Y, Xu RH. Gastric cancer treatment: recent progress and future perspectives. J Hematol Oncol. 2023 May 27;16(1):57.
- 12. Yu J, Fang T, Yun C, Liu X, Cai X. Antibody-Drug Conjugates Targeting the Human Epidermal Growth Factor Receptor Family in Cancers. Front Mol Biosci. 2022 Feb 28;9:847835.
- 13. Hofmann M, Stoss O, Shi D, Büttner R, van de Vijver M, Kim W et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008 Jun;52(7):797-805.
- 14. Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, et al; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83.
- 15. Lillemoe TJ, Rendi M, Tsai ML, Knaack M, Yarosh R, Grimm E et al. HER2 Testing Characteristics Can Predict Residual Cancer Burden Following Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer. Int J Breast Cancer. 2021 May 24;2021:6684629.
- 16. Krystel-Whittemore M, Xu J, Brogi E, Ventura K, Patil S, Ross DS et al. Pathologic complete response rate according to HER2 detection methods in HER2-positive breast cancer treated with neoadjuvant systemic therapy. Breast Cancer Res Treat. 2019 Aug;177(1):61-66.
- 17. Caselli E, Pelliccia C, Teti V, Bellezza G, Mandarano M, Ferri I et al. Looking for more reliable biomarkers in breast cancer: Comparison between routine methods and RT-qPCR. PLoS One. 2021 Sep 23;16(9):e0255580.
- 18. Sakai K, Mori S, Kawamoto T, Taniguchi S, Kobori O, Morioka Y etal. Expression of epidermal growth factor receptors on normal human gastric epithelia and gastric carcinomas. J Natl Cancer Inst. 1986 Nov;77(5):1047-52. PMID: 3464796.
- 19. Junior PN, Neto RA, Forones NM. Her2 expressıon as a prognostıc factor ın metastatıc gastrıc cancer. Arq Gastroenterol. 2016 Apr-Jun;53(2):62-7.
- 20. Yonemura Y, Ninomiya I, Yamaguchi A, Fushida S, Kimura H, Ohoyama S et al. Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short-term prognosis in gastric cancer. Cancer Res. 1991 Feb 1;51(3):1034-8. PMID: 1670998
- 21. Kim KC, Koh YW, Chang HM, Kim TH, Yook JH, Kim BS, 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 Oct;18(10):2833-40.
- 22. Feizy A, Karami A, Eghdamzamiri R, Moghimi, Taheri H, Mousavinaseb N. HER2 Expression Status and Prognostic, Diagnostic, and Demographic Properties of Patients with Gastric Cancer: a Single Center Cohort Study from Iran. Asian Pac J Cancer Prev. 2018 Jun 25;19(6):1721-1725.
- 23. Roviello G, Aprile G, D'Angelo A, Iannone LF, Roviello F, Polom K, Mini E, Catalano M. Human epidermal growth factor receptor 2 (HER2) in advanced gastric cancer: where do we stand? Gastric Cancer. 2021 Jul;24(4):765-779.
- 24. Jørgenson 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 MA, Jung EJ, Lee HS, Lee HE, Jeon YK, Yang HK et al. Evaluation of HER-2 gene status in gastric carcinoma using immunohistochemistry, fluorescence in situ hybridization, and real-time quantitative polymerase chain reaction. Hum Pathol. 2007 Sep;38(9):1386-93.
- 26. Abrahao-Machado LF, Scapulatempo-Neto C. HER2 testing in gastric cancer: An update. World J Gastroenterol. 2016 May 21;22(19):4619-25.
- 27. Rüschoff J, Nagelmeier I, Baretton G, Dietel M, Höfler H, Schildhaus HU et al. Her2-Diagnostik beim Magenkarzinom. Was ist anders im Vergleich zum Mammakarzinom? [Her2 testing in gastric cancer. What is different in comparison to breast cancer?]. Pathologe. 2010 May;31(3):208-17. German.
- 28. Wang HB, Liao XF, Zhang J. Clinicopathological factors associated with HER2-positive gastric cancer: A meta-analysis. Medicine (Baltimore). 2017 Nov;96(44):e8437.
- 29. Senel F. Clinicopathologic significance of human epidermal growth factor receptor 2 expression and gene amplification in gastric carcinoma. J Cancer Res Ther. 2022 Dec;18(Supplement):S299-S304
- 30. Baykara M, Benekli M, Ekinci O, Irkkan SC, Karaca H, Demirci U et al. Anatolian Society of Medical Oncology (ASMO). Clinical significance of HER2 overexpression in gastric and gastroesophageal junction cancers. J Gastrointest Surg. 2015 Sep;19(9):1565-71.
- 31. Uprak TK, Attaallah W, Çelikel ÇA, Ayrancı G, Yeğen C. HER-2 incidence in gastric cancer, its association with prognosis and clinicopathological parameters. J of National Surg. 2015 Aug 18;31(4):207-13.
- 32. 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: 2845-2856.
- 33. Gurbuz M, Doğan İ, Akkuş E, Karadag I, Karakaya S, Erol C et al. Clinicopathological Factors concerning HER2 Status in Metastatic Gastric Cancer: A Retrospective Observational Study Journal of oncological sciences 2022 8(1);14-19
- 34. Nergiz D, Alikanoğlu AS, Süren D, Gömceli İ, Öztürk B. Concordance of HER2 status tested by IHC and FISH in biopsy and surgical resection specimens and comparison with clinicopathological features in gastric carcinoma. Indian J Pathol Microbiol. 2022 Apr-Jun;65(2):321-327.
- 35. Giuffrè G, Ieni A, Barresi V, Caruso RA, Tuccari G. HER2 status in unusual histological variants of gastric adenocarcinomas. J Clin Pathol 2012;65: 237-241.
- 36. Risio M, De Rosa G, Sarotto I, Casorzo L, Capussotti L, Torchio B et al. HER2 testing in gastric cancer: molecular morphology and storage time-related changes in archival samples. Int J Oncol. 2003 Nov;23(5):1381-7. PMID: 14532980.
- 37. Königshoff M, Wilhelm J, Bohle RM, Pingoud A, Hahn M. HER-2/neu gene copy number quantified by real-time PCR: comparison of gene amplification, heterozygosity, and immunohistochemical status in breast cancer tissue. Clin Chem. 2003 Feb;49(2):219-29.
- 38. Dabbs DJ, Klein ME, Mohsin SK, Tubss RR, Shuai Y, Bhargava R. High false-negative rate of HER2 quantitative reverse transcription polymerase chain reaction of the Oncotype DX test: An independent quality assurance study. J Clin Oncol 2011;29(32): 4279-4285.
- 39. Lemoine NR, Jain S, Silvestre F, Lopes C, Hughes CM, McLelland E, et al. Amplification and overexpression of the EGF receptor and c-erbB-2 proto-oncogenes in human stomach cancer. Br J Cancer. 1991 Jul;64(1):79-83.
- 40. Kameda T, Yasui W, Yoshida K, Tsujino T, Nakayama H, Ito M et al. Expression of ERBB2 in human gastric carcinomas: the relationship between p185ERBB2 expression and the gene amplification. Cancer Res. 1990 Dec 15;50(24):8002-9. PMID: 1979253.
- 41. O'Malley FP, Parkes R, Latta E, Tjan S, Zadro T, Mueller R, et al. Comparison of HER2/neu status assessed by quantitative polymerase chain reaction and immunohistochemistry. Am J Clin Pathol. 2001 Apr;115(4):504-11.
- 42. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al; ToGA Trial Investigators. 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, randomized controlled trial. Lancet. 2010 Aug 28;376(9742):687-97.