clinicaloncologyКлинический случай в онкологииClinical Case in Oncology3034-14773034-4018ОНКОПРАКТИК10.62546/3034-1477-2024-2-3-7-17clinicaloncology-73Research ArticleЛЕКЦИИ И ОБЗОРЫLECTURES AND REVIEWSПроблемные аспекты оценки предиктивных маркеров при раке желудка по эндоскопическим биоптатам. Обзор литературыProblematic aspects of assessing predictive markers for gastric cancer based on endoscopic biopsy samples. Reviewhttps://orcid.org/0000-0002-9299-8706ОгурчёнокН. Е.OgurchenokN. E.

Огурчёнок Нонна Евгеньевна

198255, Санкт-Петербург, пр. Ветеранов, д. 56

Ogurchenok Nonna Evgenyevna

56 Veteranov Ave., St. Petersburg 193318

nonnapathologist@yandex.ruhttps://orcid.org/0000-0002-6322-6782АгаповМ. Ю.AgapovM. Yu.

198255, Санкт-Петербург, пр. Ветеранов, д. 56

56 Veteranov Ave., St. Petersburg 193318

https://orcid.org/0000-0002-7522-6552РаскинГ. А.RaskinG. A.

198255, Санкт-Петербург, пр. Ветеранов, д. 56; 191144, Санкт-Петербург, ул. 6-я Советская, д. 24–26; 199106, Санкт-Петербург, 21-линия В.О., д. 8а

56 Veteranov Ave., St. Petersburg 193318; 24–26 6th Sovetskaya street, St. Petersburg, 191144; 7/9 Universitetskaya Emb., St. Petersburg 199034

СПб ГБУЗ «Городской клинический онкологический диспансер»РоссияSt. Petersburg City Clinical Oncology DispensaryRussian FederationСПб ГБУЗ «Городской клинический онкологический диспансер»; ООО «Медицинский институт имени Березина Сергея»; ФГБОУ ВО «Санкт-Петербургский государственный университет»РоссияSt. Petersburg City Clinical Oncology Dispensary; Dr. Berezin Medical Insitute; St. Petersburg State UniversityRussian Federation20242701202523717Copyright © Огурчёнок Н.Е., Агапов М.Ю., Раскин Г.А., 20252025Огурчёнок Н.Е., Агапов М.Ю., Раскин Г.А.Ogurchenok N.E., Agapov M.Y., Raskin G.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.oncocase.ru/jour/article/view/73

Важным аспектом лечения пациентов с раком желудка (РЖ) является точное определение статуса рецептора эпидермального фактора роста человека 2 (HER2). HER2-позитивный рак желудка и  гастроэзофагеального соединения представляет собой агрессивный молекулярный подтип опухоли, выявляется в 5–20% случаев аденокарциномы данной локализации.

Некоторые проблемы могут возникнуть при неправильном или неточном способе забора биоптатов из опухоли и  фиксации биоптата в  формалине, что может быть обозначено как один из  ключевых факторов, которые влияют на достоверность оценки HER2.

В данной статье рассмотрены следующие аспекты:

1) забор биопсийного материала в ходе эндоскопического исследования с учетом локализации;

2) алгоритм, по которому происходит маршрутизация материала в учреждении;

3) ключевые моменты при анализе сроков фиксации материалов;

4) понимание и оценка значения экспрессии HER2 в биоптатах с РЖ.

An important aspect of the treatment of patients with gastric cancer (GC) is the accurate determination of human epidermal growth factor receptor 2 (HER2) status. HER2-positive cancer of the stomach and gastroesophageal junction is an aggressive molecular subtype of the tumor, detected in 5–20% of cases of adenocarcinoma of this localization.

Some problems may arise from incorrect or inaccurate methods of tumor biopsy and formalin fixation, which can be identified as one of the key factors that affect the reliability of HER2 assessment.

This article will cover the following aspects:

1) biopsy of histological tissue during endoscopic examination, taking into account localization;

2) the algorithm by which histological tissue is routed in the institution;

3) key points when analyzing the timing of fixation of histological tissue;

4) understanding and assessing the significance of HER2 expression in GC biopsies.

рак желудкаэндоскопияиммуногистохимияHER2фиксацияформалингетерогенностьGastric cancerendoscopyimmunohistochemistryHER2fixationformalinheterogeneityРабота выполнена без спонсорской поддержки.The work was performed without external funding.ReferencesGarattini S.K., Basile D., Cattaneo M., Fanotto V., Ongaro E. et al. Molecular classifications of gastric cancers: Novel insights and possible future applications // World J. Gastrointest. Oncol. 2017. Vol. 9. Р. 194–208. doi: 10.4251/wjgo.v9.i5.194.Garattini S.K., Basile D., Cattaneo M., Fanotto V., Ongaro E. et al. Molecular classifications of gastric cancers: Novel insights and possible future applications // World J. Gastrointest. Oncol. 2017. Vol. 9. Р. 194–208. doi: 10.4251/wjgo.v9.i5.194.Gullo I., Carneiro F., Oliveira C., Almeida G.M. Heterogeneity in Gastric Cancer: From Pure Morphology to Molecular Classifications // Pathobiology. 2017. Vol. 85. Р. 50–63. doi: 10.1159/000473881.Gullo I., Carneiro F., Oliveira C., Almeida G.M. Heterogeneity in Gastric Cancer: From Pure Morphology to Molecular Classifications // Pathobiology. 2017. Vol. 85. Р. 50–63. doi: 10.1159/000473881.Chivu-Economescu M., Matei L., Necula L.G., Dragu D.L., Bleotu C., Diaconu C.C. New therapeutic options opened by the molecular classification of gastric cancer // World J. Gastroenterol. 2018. Vol. 24. Р. 1942–1961. doi: 10.3748/wjg.v24.i18.1942.Chivu-Economescu M., Matei L., Necula L.G., Dragu D.L., Bleotu C., Diaconu C.C. New therapeutic options opened by the molecular classification of gastric cancer // World J. Gastroenterol. 2018. Vol. 24. Р. 1942–1961. doi: 10.3748/wjg.v24.i18.1942.Hess T., Maj C., Gehlen J., Borisov O., Haas S.L. et al. Dissecting the genetic heterogeneity of gastric cancer // EBioMedicine. 2023. Vol. 92. Р. 104616. https://doi.org/10.1016/j.ebiom.2023.104616.Hess T., Maj C., Gehlen J., Borisov O., Haas S.L. et al. Dissecting the genetic heterogeneity of gastric cancer // EBioMedicine. 2023. Vol. 92. Р. 104616. https://doi.org/10.1016/j.ebiom.2023.104616.Zu M., Hao X., Ning J., Zhou X., Gong Y. et al. Patient-derived organoid culture of gastric cancer for disease modeling and drug sensitivity testing // Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2023. Vol. 163. Р. 114751. https://doi.org/10.1016/j.biopha.2023.114751.Zu M., Hao X., Ning J., Zhou X., Gong Y. et al. Patient-derived organoid culture of gastric cancer for disease modeling and drug sensitivity testing // Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2023. Vol. 163. Р. 114751. https://doi.org/10.1016/j.biopha.2023.114751.Fiorillo C., Laterza V., Quero G., Menghi R. et al. From biology to surgery: One step beyond histology for tailored surgical treatments of gastric cancer // Surg. Oncol. 2020. Vol. 34. Р. 86–95. doi: 10.1016/j.suronc.2020.04.004.Fiorillo C., Laterza V., Quero G., Menghi R. et al. From biology to surgery: One step beyond histology for tailored surgical treatments of gastric cancer // Surg. Oncol. 2020. Vol. 34. Р. 86–95. doi: 10.1016/j.suronc.2020.04.004.Ho S.W.T., Tan P. Dissection of gastric cancer heterogeneity for precision oncology // Cancer Sci. 2019. Vol. 110. Р. 3405–3414. doi: 10.1111/cas.14191.Ho S.W.T., Tan P. Dissection of gastric cancer heterogeneity for precision oncology // Cancer Sci. 2019. Vol. 110. Р. 3405–3414. doi: 10.1111/cas.14191.Owen G.I., Pinto M.P., Retamal I.N., Fernádez M.F., Cisternas B. et al. Chilean Gastric Cancer Task Force. A study protocol to obtain a clinical and molecular classification of a cohort of gastric cancer patients // Medicine. 2018. Vol. 97. Р. 16. doi: 10.1097/MD.0000000000010419.Owen G.I., Pinto M.P., Retamal I.N., Fernádez M.F., Cisternas B. et al. Chilean Gastric Cancer Task Force. A study protocol to obtain a clinical and molecular classification of a cohort of gastric cancer patients // Medicine. 2018. Vol. 97. Р. 16. doi: 10.1097/MD.0000000000010419.Lei Z., Tan I.B., Das K., Deng N., Zouridis H. et al. Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil // Gastroenterology. 2013. Vol. 145. Р. 554–565. doi: 10.1053/j.gastro.2013.05.010.Lei Z., Tan I.B., Das K., Deng N., Zouridis H. et al. Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil // Gastroenterology. 2013. Vol. 145. Р. 554–565. doi: 10.1053/j.gastro.2013.05.010.Bass A.J., Thorsson V., Shmulevich I., Reynolds S.M., Miller M., Bernard B., Hinoue T. Comprehensive molecular characterization of gastric adenocarcinoma // Nature. 2014. Vol. 513. Р. 202–209. doi: 10.1038/nature13480.Bass A.J., Thorsson V., Shmulevich I., Reynolds S.M., Miller M., Bernard B., Hinoue T. Comprehensive molecular characterization of gastric adenocarcinoma // Nature. 2014. Vol. 513. Р. 202–209. doi: 10.1038/nature13480.Cristescu R., Lee J., Nebozhyn M., Kim K.M., Ting J.C., Wong S.S. et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes // Nat. Med. 2015. Vol. 21. Р. 449–456. doi: 10.1038/nm.3850.Cristescu R., Lee J., Nebozhyn M., Kim K.M., Ting J.C., Wong S.S. et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes // Nat. Med. 2015. Vol. 21. Р. 449–456. doi: 10.1038/nm.3850.Kankeu Fonkoua L., Yee N.S. Molecular Characterization of Gastric Carcinoma: Therapeutic Implications for Biomarkers and Targets // Biomedicines. 2018. Vol. 6. Р. 32. doi: 10.3390/biomedicines6010032.Kankeu Fonkoua L., Yee N.S. Molecular Characterization of Gastric Carcinoma: Therapeutic Implications for Biomarkers and Targets // Biomedicines. 2018. Vol. 6. Р. 32. doi: 10.3390/biomedicines6010032.Ichikawa H., Nagahashi M., Shimada Y., Hanyu T., Ishikawa T. et al. Actionable gene-based classification toward precision medicine in gastric cancer // Genome Med. 2017. Vol. 9. Р. 93. doi: 10.1186/s13073-017-0484-3.Ichikawa H., Nagahashi M., Shimada Y., Hanyu T., Ishikawa T. et al. Actionable gene-based classification toward precision medicine in gastric cancer // Genome Med. 2017. Vol. 9. Р. 93. doi: 10.1186/s13073-017-0484-3.Carlomagno N., Incollingo P., Tammaro V., Peluso G., Rupealta N. et al. Diagnostic, Predictive, Prognostic, and Therapeutic Molecular Biomarkers in Third Millennium: A Breakthrough in Gastric Cancer // Biomed. Res. Int. 2017. Vol. 2017. Р. 7869802. doi: 10.1155/2017/7869802.Carlomagno N., Incollingo P., Tammaro V., Peluso G., Rupealta N. et al. Diagnostic, Predictive, Prognostic, and Therapeutic Molecular Biomarkers in Third Millennium: A Breakthrough in Gastric Cancer // Biomed. Res. Int. 2017. Vol. 2017. Р. 7869802. doi: 10.1155/2017/7869802.Matsuoka T., Yashiro M. Biomarkers of gastric cancer: Current topics and future perspective // World J. Gastroenterol. 2018. Vol. 24. Р. 2818–2832. doi: 10.3748/wjg.v24.i26.2818.Matsuoka T., Yashiro M. Biomarkers of gastric cancer: Current topics and future perspective // World J. Gastroenterol. 2018. Vol. 24. Р. 2818–2832. doi: 10.3748/wjg.v24.i26.2818.Guan W.L., He Y., Xu R.H. Gastric cancer treatment: recent progress and future perspectives // Journal of hematology & oncology. 2023. Vol. 16, No. 1. Р. 57. https://doi.org/10.1186/s13045-023-01451-3.Guan W.L., He Y., Xu R.H. Gastric cancer treatment: recent progress and future perspectives // Journal of hematology & oncology. 2023. Vol. 16, No. 1. Р. 57. https://doi.org/10.1186/s13045-023-01451-3.Saraggi D., Fassan M., Bornschein J., Farinati F., Realdon S., Valeri N., Rugge M. From Barrett metaplasia to esophageal adenocarcinoma: the molecular background // Histol. Histopathol. 2016. Jan. Vol. 31, No. 1. Р. 25–32. Epub 2015 Sep 3. PMID: 26334343.Saraggi D., Fassan M., Bornschein J., Farinati F., Realdon S., Valeri N., Rugge M. From Barrett metaplasia to esophageal adenocarcinoma: the molecular background // Histol. Histopathol. 2016. Jan. Vol. 31, No. 1. Р. 25–32. Epub 2015 Sep 3. PMID: 26334343.Sugano K., Moss S.F., Kuipers E.J. Gastric Intestinal Metaplasia: Real Culprit or Innocent Bystander as a Precancerous Condition for Gastric Cancer? // Gastroenterology. 2023. Vol. 165, No. 6. Р. 1352–1366.e1. https://doi.org/10.1053/j.gastro.2023.08.028.Sugano K., Moss S.F., Kuipers E.J. Gastric Intestinal Metaplasia: Real Culprit or Innocent Bystander as a Precancerous Condition for Gastric Cancer? // Gastroenterology. 2023. Vol. 165, No. 6. Р. 1352–1366.e1. https://doi.org/10.1053/j.gastro.2023.08.028.Fassan M., Mastracci L., Grillo F., Zagonel V., Bruno S. еt al. Early HER2 dysregulation in gastric and oesophageal carcinogenesis // Histopathology. 2012. Nov. Vol. 61, No. 5. Р. 769–776. doi: 10.1111/j.1365–2559.2012.04272.x. Epub 2012 Aug 9. PMID: 22882541.Fassan M., Mastracci L., Grillo F., Zagonel V., Bruno S. еt al. Early HER2 dysregulation in gastric and oesophageal carcinogenesis // Histopathology. 2012. Nov. Vol. 61, No. 5. Р. 769–776. doi: 10.1111/j.1365–2559.2012.04272.x. Epub 2012 Aug 9. PMID: 22882541.Qiao J., Feng M., Zhou W., Tan Y., Yang S. еt al. YAP inhibition overcomes adaptive resistance in HER2-positive gastric cancer treated with trastuzumab via the AKT/mTOR and ERK/mTOR axis // Gastric cancer: official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2024. Vol. 27, No. 4. Р. 785–801. https://doi.org/10.1007/s10120-024-01508-3.Qiao J., Feng M., Zhou W., Tan Y., Yang S. еt al. YAP inhibition overcomes adaptive resistance in HER2-positive gastric cancer treated with trastuzumab via the AKT/mTOR and ERK/mTOR axis // Gastric cancer: official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2024. Vol. 27, No. 4. Р. 785–801. https://doi.org/10.1007/s10120-024-01508-3.Fassan M., Pizzi M., Realdon S., Balistreri M., Guzzardo V. et al. The HER2-miR125a5p/miR125b loop in gastric and esophageal carcinogenesis // Hum. Pathol. 2013. Sep. Vol. 44. No. 9. Р. 1804–1810. doi: 10.1016/j.humpath.2013.01.023. Epub 2013 Apr 22. PMID: 23618359.Fassan M., Pizzi M., Realdon S., Balistreri M., Guzzardo V. et al. The HER2-miR125a5p/miR125b loop in gastric and esophageal carcinogenesis // Hum. Pathol. 2013. Sep. Vol. 44. No. 9. Р. 1804–1810. doi: 10.1016/j.humpath.2013.01.023. Epub 2013 Apr 22. PMID: 23618359.Yarden Y., Sliwkowski M.X. Untangling the ErbB signaling network // Nat. Rev. Mol. Cell Biol. 2001. V. 2. P. 127–135.Yarden Y., Sliwkowski M.X. Untangling the ErbB signaling network // Nat. Rev. Mol. Cell Biol. 2001. V. 2. P. 127–135.Olayiloye M.A., Neve R.M., Lane H.A. et al. The ErbB signaling network: receptor heterodimerization in development and cancer // EMBO J. 2000. Vol. 19. P. 3159–3167.Olayiloye M.A., Neve R.M., Lane H.A. et al. The ErbB signaling network: receptor heterodimerization in development and cancer // EMBO J. 2000. Vol. 19. P. 3159–3167.Thor A.D., Liu S., Edgerson S. et al. Activation (tyrosine phosphorylation) of ErbB2 (HER2/neu): a study of incidence and correlation with outcome in breast cancer // J. Clin. Oncol. 2000. Vol. 18. P. 3230–9;Thor A.D., Liu S., Edgerson S. et al. Activation (tyrosine phosphorylation) of ErbB2 (HER2/neu): a study of incidence and correlation with outcome in breast cancer // J. Clin. Oncol. 2000. Vol. 18. P. 3230–9;Djaballah S.A. et al. HER2 in Colorectal Cancer: The Long and Winding Road From Negative Predictive Factor to Positive Actionable Target // Am. Soc. Clin. Oncol. Educ Book. 2022. Vol. 42. Р. 219–232. doi: 10.1200/EDBK_351354.Djaballah S.A. et al. HER2 in Colorectal Cancer: The Long and Winding Road From Negative Predictive Factor to Positive Actionable Target // Am. Soc. Clin. Oncol. Educ Book. 2022. Vol. 42. Р. 219–232. doi: 10.1200/EDBK_351354.Bai X., Sun P., Wang X. et al. Structure and dynamics of the EGFR/HER2 heterodimer // Cell Discov. 2023. Vol. 9, No. 18. https://doi.org/10.1038/s41421-023-00523-5.Bai X., Sun P., Wang X. et al. Structure and dynamics of the EGFR/HER2 heterodimer // Cell Discov. 2023. Vol. 9, No. 18. https://doi.org/10.1038/s41421-023-00523-5.Guo L.W., Li X.G., Yang Y.S., Lu X.X., Han X.C. et al. Large-scale genomic sequencing reveals adaptive opportunity of targeting mutated-PI3K in early and advanced HER2-positive breast cancer // Clin. Transl. Med. 2021. Nov. Vol. 11, No. 11. Р. e589. doi: 10.1002/ctm2.589. PMID: 34842356; PMCID: PMC8567053.Guo L.W., Li X.G., Yang Y.S., Lu X.X., Han X.C. et al. Large-scale genomic sequencing reveals adaptive opportunity of targeting mutated-PI3K in early and advanced HER2-positive breast cancer // Clin. Transl. Med. 2021. Nov. Vol. 11, No. 11. Р. e589. doi: 10.1002/ctm2.589. PMID: 34842356; PMCID: PMC8567053.Fanotto V., Ongaro E., Rihawi K., Avallone A., Silvestris N. et al. HER-2 inhibition in gastric and colorectal cancers: tangible achievements, novel acquisitions and future perspectives // Oncotarget. 2016. Vol. 7, No. 42. Р. 69060– 69074. https://doi.org/10.18632/oncotarget.11264.Fanotto V., Ongaro E., Rihawi K., Avallone A., Silvestris N. et al. HER-2 inhibition in gastric and colorectal cancers: tangible achievements, novel acquisitions and future perspectives // Oncotarget. 2016. Vol. 7, No. 42. Р. 69060– 69074. https://doi.org/10.18632/oncotarget.11264.Birkman E.M., Mansuri N., Kurki S., Ålgars A., Lintunen M., Ristamäki R., Sundström J., Carpén O. Gastric cancer: Immunohistochemical classification of molecular subtypes and their association with clinicopathological characteristics // Virchows Arch. 2018. Vol. 472. Р. 369–382. doi: 10.1007/s00428-017-2240-x.Birkman E.M., Mansuri N., Kurki S., Ålgars A., Lintunen M., Ristamäki R., Sundström J., Carpén O. Gastric cancer: Immunohistochemical classification of molecular subtypes and their association with clinicopathological characteristics // Virchows Arch. 2018. Vol. 472. Р. 369–382. doi: 10.1007/s00428-017-2240-x.Wang Q., Liu G., Hu C. Molecular Classification of Gastric Adenocarcinoma // Gastroenterology research. 2019. Vol. 12, No. 6. Р. 275–282.Wang Q., Liu G., Hu C. Molecular Classification of Gastric Adenocarcinoma // Gastroenterology research. 2019. Vol. 12, No. 6. Р. 275–282.Marano L., Roviello F. The distinctive nature of HER2-positive gastric cancers // European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2015. Vol. 41, No. 3. Р. 271–273. https://doi.org/10.1016/j.ejso.2014.12.007 https://doi.org/10.14740/gr1187.Marano L., Roviello F. The distinctive nature of HER2-positive gastric cancers // European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2015. Vol. 41, No. 3. Р. 271–273. https://doi.org/10.1016/j.ejso.2014.12.007 https://doi.org/10.14740/gr1187.Lindor N.M., Burgart L.J., Leontovich O., Goldberg R.M., Cunningham J.M. et al. Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors // J. Clin. Oncol. 2002. Vol. 20. P. 1043–1048. doi: 10.1200/JCO.2002.20.4.1043.Lindor N.M., Burgart L.J., Leontovich O., Goldberg R.M., Cunningham J.M. et al. Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors // J. Clin. Oncol. 2002. Vol. 20. P. 1043–1048. doi: 10.1200/JCO.2002.20.4.1043.Mathiak M., Warneke V.S., Behrens H.M., Haag J., Böger C. et al. Clinicopathologic Characteristics of Microsatellite Instable Gastric Carcinomas Revisited: Urgent Need for Standardization // Applied immunohistochemistry & molecular morphology: AIMM. 2017. Vol. 25, No. 1. Р. 12–24. https://doi.org/10.1097/PAI.0000000000000264.Mathiak M., Warneke V.S., Behrens H.M., Haag J., Böger C. et al. Clinicopathologic Characteristics of Microsatellite Instable Gastric Carcinomas Revisited: Urgent Need for Standardization // Applied immunohistochemistry & molecular morphology: AIMM. 2017. Vol. 25, No. 1. Р. 12–24. https://doi.org/10.1097/PAI.0000000000000264.Smyth E.C., Wotherspoon A., Peckitt C., Gonzalez D., Hulkki-Wilson S. et al. Mismatch Repair Deficiency, Microsatellite Instability, and Survival: An Exploratory Analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) Trial // JAMA oncology. 2017. Vol. 3, No. 9. Р. 1197–1203. https://doi.org/10.1001/jamaoncol.2016.6762.Smyth E.C., Wotherspoon A., Peckitt C., Gonzalez D., Hulkki-Wilson S. et al. Mismatch Repair Deficiency, Microsatellite Instability, and Survival: An Exploratory Analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) Trial // JAMA oncology. 2017. Vol. 3, No. 9. Р. 1197–1203. https://doi.org/10.1001/jamaoncol.2016.6762.Choi Y.Y., Kim H., Shin S.J., Kim H.Y., Lee J. et al. Microsatellite Instability and Programmed Cell Death-Ligand 1 Expression in Stage II/III Gastric Cancer: Post Hoc Analysis of the CLASSIC Randomized Controlled study // Annals of surgery. 2019. Vol. 270, No. 2. Р. 309–316. https://doi.org/10.1097/SLA.0000000000002803.Choi Y.Y., Kim H., Shin S.J., Kim H.Y., Lee J. et al. Microsatellite Instability and Programmed Cell Death-Ligand 1 Expression in Stage II/III Gastric Cancer: Post Hoc Analysis of the CLASSIC Randomized Controlled study // Annals of surgery. 2019. Vol. 270, No. 2. Р. 309–316. https://doi.org/10.1097/SLA.0000000000002803.Grillo F., Fassan M., Sarocchi F., Fiocca R., Mastracci L. HER2 heterogeneity in gastric/gastroesophageal cancers: From benchside to practice // World J. Gastroenterol. 2016. Jul 14. Vol. 22, No. 26. Р. 5879–5887.Grillo F., Fassan M., Sarocchi F., Fiocca R., Mastracci L. HER2 heterogeneity in gastric/gastroesophageal cancers: From benchside to practice // World J. Gastroenterol. 2016. Jul 14. Vol. 22, No. 26. Р. 5879–5887.Subasinghe D., Acott N., Kumarasinghe M.P. A survival guide to HER2 testing in gastric/gastroesophageal junction carcinoma // Gastrointest. Endosc. 2019. Jul. Vol. 90, No. 1. Р. 44–54.Subasinghe D., Acott N., Kumarasinghe M.P. A survival guide to HER2 testing in gastric/gastroesophageal junction carcinoma // Gastrointest. Endosc. 2019. Jul. Vol. 90, No. 1. Р. 44–54.Бесова Н.С., Калинин А.Е., Неред С.Н., Трякин А.А., Гамаюнов С.В. и др. Рак желудка. Клинические рекомендации // Современная онкология. 2021. Т. 23, № 4. С. 541–571.Besova N.S., Kalinin A.E., Nered S.N., Tryakin A.A., Gamayunov S.V. and others. Stomach cancer. Clinical recommendations. Modern oncology. 2021, Vol. 23, No. 4, pp. 541–571 (In Russ.)]. doi: 10.26442/18151434.2021.4.201239.Gullo I., Grillo F., Molinaro L., Fassan M., De Silvestri A. et al. Minimum biopsy set for HER2 evaluation in gastric and gastro-esophageal junction cancer // Endosc. Int. Open. 2015. Apr. Vol. 3, No. 2. Р. E165–70.Gullo I., Grillo F., Molinaro L., Fassan M., De Silvestri A. et al. Minimum biopsy set for HER2 evaluation in gastric and gastro-esophageal junction cancer // Endosc. Int. Open. 2015. Apr. Vol. 3, No. 2. Р. E165–70.Tominaga N., Gotoda T., Hara M., Hale M.D., Tsuchiya T. et al. Five biopsy specimens from the proximal part of the tumor reliably determine HER2 protein expression status in gastric cancer // Gastric Cancer. 2016. Apr. Vol. 19, No. 2. Р. 553–560.Tominaga N., Gotoda T., Hara M., Hale M.D., Tsuchiya T. et al. Five biopsy specimens from the proximal part of the tumor reliably determine HER2 protein expression status in gastric cancer // Gastric Cancer. 2016. Apr. Vol. 19, No. 2. Р. 553–560.Xu C., Liu Y., Ge X., Jiang D., Zhang Y. еt al. Tumor containing fragment number influences immunohistochemistry positive rate of HER2 in biopsy specimens of gastric cancer // Diagn. Pathol. 2017. May 26. Vol. 12, No. 1. Р. 41.Xu C., Liu Y., Ge X., Jiang D., Zhang Y. еt al. Tumor containing fragment number influences immunohistochemistry positive rate of HER2 in biopsy specimens of gastric cancer // Diagn. Pathol. 2017. May 26. Vol. 12, No. 1. Р. 41.Kumarasinghe M.P., Morey A., Bilous M., Farshid G., Francis G. еt al. HER2 testing in advanced gastric and gastrooesophageal cancer: analysis of an Australia-wide testing program // Pathology. 2017. Oct. Vol. 49, No. 6. Р. 575–581.Kumarasinghe M.P., Morey A., Bilous M., Farshid G., Francis G. еt al. HER2 testing in advanced gastric and gastrooesophageal cancer: analysis of an Australia-wide testing program // Pathology. 2017. Oct. Vol. 49, No. 6. Р. 575–581.Kaye P., Lindsay D., Madhusudan S., Vohra R., Catton J., Platt C., Ragunath K. Upper GI biopsies for adenocarcinoma — how many biopsies should endoscopists take? // Histopathology. 2019. May. Vol. 74, No. 6. Р. 959–963.Kaye P., Lindsay D., Madhusudan S., Vohra R., Catton J., Platt C., Ragunath K. Upper GI biopsies for adenocarcinoma — how many biopsies should endoscopists take? // Histopathology. 2019. May. Vol. 74, No. 6. Р. 959–963.Bang Y.J., Van Cutsem E., Feyereislova A., Chung H.C., Shen L. 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. Vol. 376. Р. 687–697.Bang Y.J., Van Cutsem E., Feyereislova A., Chung H.C., Shen L. 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. Vol. 376. Р. 687–697.Oono Y., Kuwata T., Takashima K., Shinmura K., Hori K. еt al. Human epidermal growth factor receptor 2-, epidermal growth factor receptor-, and mesenchymal epithelial transition factor-positive sites of gastric cancer using surgical samples // Gastric Cancer. 2019. Mar. Vol. 22, No. 2. Р 335–343.Oono Y., Kuwata T., Takashima K., Shinmura K., Hori K. еt al. Human epidermal growth factor receptor 2-, epidermal growth factor receptor-, and mesenchymal epithelial transition factor-positive sites of gastric cancer using surgical samples // Gastric Cancer. 2019. Mar. Vol. 22, No. 2. Р 335–343.Sauter G., Lee J., Bartlett J.M., Slamon D.J., Press M.F. Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations // Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2009. Vol. 27, No. 8. Р. 1323–1333. https://doi.org/10.1200/JCO.2007.14.8197.Sauter G., Lee J., Bartlett J.M., Slamon D.J., Press M.F. Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations // Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2009. Vol. 27, No. 8. Р. 1323–1333. https://doi.org/10.1200/JCO.2007.14.8197.Yanagimoto Y., Imamura H., Adachi S., Odagiri K., Kawase T. еt al. The effect of specimen processing time on HER2 expression in gastric cancer and esophagogastric junction cancer: a single-center retrospective observational study // BMC Cancer. 2023. Jul. 11. Vol. 23, No. 1. Р. 645.Yanagimoto Y., Imamura H., Adachi S., Odagiri K., Kawase T. еt al. The effect of specimen processing time on HER2 expression in gastric cancer and esophagogastric junction cancer: a single-center retrospective observational study // BMC Cancer. 2023. Jul. 11. Vol. 23, No. 1. Р. 645.Мальков П.Г., Франк Г.А., Данилова Н.В., Москвина Л.В., Завалишина Л.Э. Основы обеспечения качества в гистологической лабораторной технике: руководство / под ред. П. Г. Малькова, Г. А. Франка. М., 2011. 108 с.Malkov P.G., Frank G.A., Danilova N.V., Moskvina L.V., Zavalishina L.E. Fundamentals of quality assurance in histological laboratory technology: a manual / ed. P. G. Malkova, G. A. Frank. Moscow., 2011. 108 p. (In Russ.)Nakamura M., Watanabe A., Yoshizawa A., Iwasaki S., Nomura A. еt al. The risk of weekend biopsy: Impact of specimen source and fixation status on HER2 assessment in the treatment of advanced gastric cancer (The HER_WEEKEND study) // Pathol. Int. 2023. Oct. Vol. 73, No. 10. Р. 509–519.Nakamura M., Watanabe A., Yoshizawa A., Iwasaki S., Nomura A. еt al. The risk of weekend biopsy: Impact of specimen source and fixation status on HER2 assessment in the treatment of advanced gastric cancer (The HER_WEEKEND study) // Pathol. Int. 2023. Oct. Vol. 73, No. 10. Р. 509–519.Bartley A.N., Washington M.K., Colasacco C., Ventura C.B., Ismaila N. 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 // Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2017. Vol. 35, No. 4. Р. 446–464. https://doi.org/10.1200/JCO.2016.69.4836.Bartley A.N., Washington M.K., Colasacco C., Ventura C.B., Ismaila N. 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 // Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2017. Vol. 35, No. 4. Р. 446–464. https://doi.org/10.1200/JCO.2016.69.4836.Likhithaswamy H.R., Madhushankari G.S., Selvamani M., Mohan Kumar K.P., Kokila G., Mahalakshmi S. Assessing the Quality of Long-Term Stored Tissues in Formalin and in Paraffin-Embedded Blocks for Histopathological Analysis // J. Microsc. Ultrastruct. 2022. Feb 4. Vol. 10, No. 1. Р. 23–29. doi: 10.4103/JMAU.JMAU_53_20. PMID: 35433260. Vol. PMCID: PMC9012411.Likhithaswamy H.R., Madhushankari G.S., Selvamani M., Mohan Kumar K.P., Kokila G., Mahalakshmi S. Assessing the Quality of Long-Term Stored Tissues in Formalin and in Paraffin-Embedded Blocks for Histopathological Analysis // J. Microsc. Ultrastruct. 2022. Feb 4. Vol. 10, No. 1. Р. 23–29. doi: 10.4103/JMAU.JMAU_53_20. PMID: 35433260. Vol. PMCID: PMC9012411.Grillo F., Pigozzi S., Ceriolo P., Calamaro P., Fiocca R., Mastracci L. Factors affecting immunoreactivity in long-term storage of formalin-fixed paraffin-embedded tissue sections // Histochem Cell Biol. 2015. Jul. Vol. 144, No. 1. Р. 93– 99. doi: 10.1007/s00418-015-1316-4. Epub 2015. Mar 11. PMID: 25757745.Grillo F., Pigozzi S., Ceriolo P., Calamaro P., Fiocca R., Mastracci L. Factors affecting immunoreactivity in long-term storage of formalin-fixed paraffin-embedded tissue sections // Histochem Cell Biol. 2015. Jul. Vol. 144, No. 1. Р. 93– 99. doi: 10.1007/s00418-015-1316-4. Epub 2015. Mar 11. PMID: 25757745.Dietel M., Ellis I.O., Höfler H., Kreipe H., Moch H. еt al. Comparison of automated silver enhanced in situ hybridisation (SISH) and fluorescence ISH (FISH) for the validation of HER2 gene status in breast carcinoma according to the guidelines of the American Society of Clinical Oncology and the College of American Pathologists // Virchows Arch. 2007. Jul. Vol. 451, No. 1. Р. 9–25. doi: 10.1007/s00428-007-0424-5. Epub 2007. Jun 12. PMID: 17562074.Dietel M., Ellis I.O., Höfler H., Kreipe H., Moch H. еt al. Comparison of automated silver enhanced in situ hybridisation (SISH) and fluorescence ISH (FISH) for the validation of HER2 gene status in breast carcinoma according to the guidelines of the American Society of Clinical Oncology and the College of American Pathologists // Virchows Arch. 2007. Jul. Vol. 451, No. 1. Р. 9–25. doi: 10.1007/s00428-007-0424-5. Epub 2007. Jun 12. PMID: 17562074.Nicole McMillian N., Lenora Pluchino M.A., Ajani J.A., D T.A., Chair V., Bentrem D.J. et al. NCCN Guidelines Version 2. 2022. Gastric Cancer. 2022.Nicole McMillian N., Lenora Pluchino M.A., Ajani J.A., D T.A., Chair V., Bentrem D.J. et al. NCCN Guidelines Version 2. 2022. Gastric Cancer. 2022.Jung J., Kim S.T., Ko J., Hong J.Y., Park J.O., Ha S.Y., Lee J. Clinical Implication of HER2 Aberration in Patients With Metastatic Cancer Using Next-Generation Sequencing: A Pan-Tumor Analysis // JCO Precis Oncol. 2023. Jul. Vol. 7. e2200537. doi: 10.1200/PO.22.00537. PMID: 37499191.Jung J., Kim S.T., Ko J., Hong J.Y., Park J.O., Ha S.Y., Lee J. Clinical Implication of HER2 Aberration in Patients With Metastatic Cancer Using Next-Generation Sequencing: A Pan-Tumor Analysis // JCO Precis Oncol. 2023. Jul. Vol. 7. e2200537. doi: 10.1200/PO.22.00537. PMID: 37499191.Hofmann M., Stoss O., Shi D., Büttner R., van de Vijver M. et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study // Histopathology. 2008. Vol. 52, No. 7. Р. 797–805. https://doi.org/10.1111/j.1365-2559.2008.03028.x.Hofmann M., Stoss O., Shi D., Büttner R., van de Vijver M. et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study // Histopathology. 2008. Vol. 52, No. 7. Р. 797–805. https://doi.org/10.1111/j.1365-2559.2008.03028.x.Van Cutsem E., Bang Y.J., Feng-Yi F., Xu J.M., Lee K.W. et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer // Gastric cancer: official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2015. Vol. 18, No. 3. Р. 476–484. https://doi.org/10.1007/s10120-014-0402-yVan Cutsem E., Bang Y.J., Feng-Yi F., Xu J.M., Lee K.W. et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer // Gastric cancer: official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2015. Vol. 18, No. 3. Р. 476–484. https://doi.org/10.1007/s10120-014-0402-yAhn S., Van Vrancken M., Lee M., Ha S.Y., Lee H. et al. Ideal number of biopsy tumor fragments for predicting HER2 status in gastric carcinoma resection specimens // Oncotarget. 2015. Vol. 6, No. 35. Р. 38372–38380. https://doi.org/10.18632/oncotarget.5368.Ahn S., Van Vrancken M., Lee M., Ha S.Y., Lee H. et al. Ideal number of biopsy tumor fragments for predicting HER2 status in gastric carcinoma resection specimens // Oncotarget. 2015. Vol. 6, No. 35. Р. 38372–38380. https://doi.org/10.18632/oncotarget.5368.Rüschoff J., Dietel M., Baretton G., Arbogast S., Walch A. HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing // Virchows Archiv: an international journal of pathology. 2010. Vol. 457, No. 3. Р. 299–307. https://doi.org/10.1007/s00428-010-0952-2.Rüschoff J., Dietel M., Baretton G., Arbogast S., Walch A. HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing // Virchows Archiv: an international journal of pathology. 2010. Vol. 457, No. 3. Р. 299–307. https://doi.org/10.1007/s00428-010-0952-2.Grillo F., Fassan M., Ceccaroli C., Giacometti C., Curto M. et al. The Reliability of Endoscopic Biopsies in Assessing HER2 Status in Gastric and Gastroesophageal Junction Cancer: A Study Comparing Biopsies with Surgical Samples // Translational oncology. 2013. Vol. 6, No. 1. Р. 10–16. https://doi.org/10.1593/tlo.12334.Grillo F., Fassan M., Ceccaroli C., Giacometti C., Curto M. et al. The Reliability of Endoscopic Biopsies in Assessing HER2 Status in Gastric and Gastroesophageal Junction Cancer: A Study Comparing Biopsies with Surgical Samples // Translational oncology. 2013. Vol. 6, No. 1. Р. 10–16. https://doi.org/10.1593/tlo.12334.Yang J., Luo H., Li Y., Li J., Cai Z. et al. Intratumoral heterogeneity determines discordant results of diagnostic tests for human epidermal growth factor receptor (HER) 2 in gastric cancer specimens // Cell biochemistry and biophysics. 2012. Vol. 62, No. 1. Р. 221–228. https://doi.org/10.1007/s12013-011-9286-1.Yang J., Luo H., Li Y., Li J., Cai Z. et al. Intratumoral heterogeneity determines discordant results of diagnostic tests for human epidermal growth factor receptor (HER) 2 in gastric cancer specimens // Cell biochemistry and biophysics. 2012. Vol. 62, No. 1. Р. 221–228. https://doi.org/10.1007/s12013-011-9286-1.Kumarasinghe A.P., de Boer B., Bateman A.C., Kumarasinghe M.P. DNA mismatch repair enzyme immunohistochemistry in colorectal cancer: a comparison of biopsy and resection material // Pathology. 2010. Vol. 42, No. 5. Р. 414– 420. https://doi.org/10.3109/00313025.2010.493862.Kumarasinghe A.P., de Boer B., Bateman A.C., Kumarasinghe M.P. DNA mismatch repair enzyme immunohistochemistry in colorectal cancer: a comparison of biopsy and resection material // Pathology. 2010. Vol. 42, No. 5. Р. 414– 420. https://doi.org/10.3109/00313025.2010.493862.Park S.R., Park Y.S., Ryu M.H., Ryoo B.Y., Woo C.G. et al. Extra-gain of HER2-positive cases through HER2 reassessment in primary and metastatic sites in advanced gastric cancer with initially HER2-negative primary tumours: Results of GASTric cancer HER2 reassessment study 1 (GASTHER1) // European journal of cancer (Oxford, England). 2016. Vol. 53. Р. 42–50. https://doi.org/10.1016/j.ejca.2015.09.018.Park S.R., Park Y.S., Ryu M.H., Ryoo B.Y., Woo C.G. et al. Extra-gain of HER2-positive cases through HER2 reassessment in primary and metastatic sites in advanced gastric cancer with initially HER2-negative primary tumours: Results of GASTric cancer HER2 reassessment study 1 (GASTHER1) // European journal of cancer (Oxford, England). 2016. Vol. 53. Р. 42–50. https://doi.org/10.1016/j.ejca.2015.09.018.Lee S., de Boer W.B., Fermoyle S., Platten M., Kumarasinghe M.P. Human epidermal growth factor receptor 2 testing in gastric carcinoma: issues related to heterogeneity in biopsies and resections // Histopathology. 2011. Vol. 59, No. 5. Р. 832–840. https://doi.org/10.1111/j.1365-2559.2011.04017.xLee S., de Boer W.B., Fermoyle S., Platten M., Kumarasinghe M.P. Human epidermal growth factor receptor 2 testing in gastric carcinoma: issues related to heterogeneity in biopsies and resections // Histopathology. 2011. Vol. 59, No. 5. Р. 832–840. https://doi.org/10.1111/j.1365-2559.2011.04017.xWatson S., Validire P., Cervera P., Zorkani N., Scriva A. et al. Combined HER2 analysis of biopsies and surgical specimens to optimize detection of trastuzumab-eligible patients in eso-gastric adenocarcinoma: a GERCOR study // Annals of oncology: official journal of the European Society for Medical Oncology. 2013. Vol. 24, No. 2. Р. 3035–3039. https://doi.org/10.1093/annonc/mdt393.Watson S., Validire P., Cervera P., Zorkani N., Scriva A. et al. Combined HER2 analysis of biopsies and surgical specimens to optimize detection of trastuzumab-eligible patients in eso-gastric adenocarcinoma: a GERCOR study // Annals of oncology: official journal of the European Society for Medical Oncology. 2013. Vol. 24, No. 2. Р. 3035–3039. https://doi.org/10.1093/annonc/mdt393.

The authors declare that there are no conflicts of interest present.