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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">anatomy</journal-id><journal-title-group><journal-title xml:lang="ru">Журнал анатомии и гистопатологии</journal-title><trans-title-group xml:lang="en"><trans-title>Journal of Anatomy and Histopathology</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2225-7357</issn><publisher><publisher-name>N.N. Burdenko Voronezh State Medical University</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.18499/2225-7357-2023-12-4-68-75</article-id><article-id custom-type="elpub" pub-id-type="custom">anatomy-1840</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL PAPERS</subject></subj-group></article-categories><title-group><article-title>Оценка связи PD-L1-статуса, выявляемого клонами SP142 и SP263, с клинико-морфологическими характеристиками рака желудка</article-title><trans-title-group xml:lang="en"><trans-title>Association Between PD-L1 status Detected by SP142 and SP263 Antibody Clones and Clinical and Morphological Features of Gastric Cancer Factors</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6482-1110</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сотникова</surname><given-names>Т. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Sotnikova</surname><given-names>T. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Сотникова Татьяна Николаевна – заведующий патологоанатомическим отделением</p><p>ул. Яузская, 11, Москва, 109240</p></bio><bio xml:lang="en"><p>Tat’yana N. Sotnikova – Head of the Department of Pathology</p><p>ul. Yauzskaya, 11, Moscow, 109240</p></bio><email xlink:type="simple">docsotnikova@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7458-991X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Полушкина</surname><given-names>Т. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Polushkina</surname><given-names>T. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Полушкина Татьяна Валерьевна – врач-патологоанатом</p><p>Москва</p></bio><bio xml:lang="en"><p>Tat’yana V. Polushkina – Doctor at the Department of Pathology </p><p>Moscow</p></bio><email xlink:type="simple">peperonya1173@yandex.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6247-9481</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Калинин</surname><given-names>Д. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Kalinin</surname><given-names>D. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Калинин Дмитрий Валерьевич – канд. мед. наук, заведующий патологоанатомическим отделением</p><p>Москва</p></bio><bio xml:lang="en"><p>Dmitrii V. Kalinin – Cand. Sci. (Med.), Head of the Department of Pathology</p><p>Moscow</p></bio><email xlink:type="simple">dmitry.v.kalinin@gmail.com</email><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7848-6707</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Данилова</surname><given-names>Н. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Danilova</surname><given-names>N. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Данилова Наталья Владимировна – д-р мед. наук, старший научн. сотр. отдела клинической патологии</p><p>Москва</p></bio><bio xml:lang="en"><p>Natal’ya V. Danilova – Doct. Sci. (Med.), senior researcher </p><p>Moscow</p></bio><email xlink:type="simple">natalyadanilova@gmail.com</email><xref ref-type="aff" rid="aff-4"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Городская клиническая больница им. И.В. Давыдовского</institution></aff><aff xml:lang="en"><institution>I.V. Davydovsky Municipal Clinical Hospital</institution></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Московский государственный университет им. М.В. Ломоносова</institution></aff><aff xml:lang="en"><institution>M.V. Lomonosov Moscow State University</institution></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>Городская клиническая больница им. И.В. Давыдовского; Московский государственный университет им. М.В. Ломоносова</institution></aff><aff xml:lang="en"><institution>I.V. Davydovsky Municipal Clinical Hospital; M.V. Lomonosov Moscow State University</institution></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru"><institution>Национальный медицинский исследовательский центр хирургии им. А.В. Вишневского</institution></aff><aff xml:lang="en"><institution>A.V. Vishnevsky National Medical Research Center for Surgery</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2023</year></pub-date><pub-date pub-type="epub"><day>19</day><month>01</month><year>2024</year></pub-date><volume>12</volume><issue>4</issue><fpage>68</fpage><lpage>75</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Сотникова Т.Н., Полушкина Т.В., Калинин Д.В., Данилова Н.В., 2024</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="ru">Сотникова Т.Н., Полушкина Т.В., Калинин Д.В., Данилова Н.В.</copyright-holder><copyright-holder xml:lang="en">Sotnikova T.N., Polushkina T.V., Kalinin D.V., Danilova N.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://anatomy.elpub.ru/jour/article/view/1840">https://anatomy.elpub.ru/jour/article/view/1840</self-uri><abstract><p>Целью исследования – изучение связи PD-L1-статуса при использовании клонов SP142 и SP263 в раке желудка с его клинико-морфологическими параметрами. Материал и методы. Операционный материал, полученный от 131 пациента с подтвержденным диагнозом рака желудка. Антителами к PD-L1 клона SP263 были окрашены 127 случаев, антителами к PD-L1 клона SP142 – 126 случаев. Постановку реакций с PD-L1 осуществляли с помощью прибора Ventana BenchMark Ultra (Roche Ventana, USA) по рекомендованным производителем первичных антител протоколам. Результаты иммуногистохимического окрашивания сопоставлены с клинико-морфологическими характеристиками рака желудка с применением статистического анализа. Результаты. Положительный PD-L1-статус, выявленный клонами SP263 и SP142, значимо ассоциирован со 2-м типом по макроскопической формой по классификации R. Bormann (p=0,003/p=0,003), тубулярным морфологическим типом по классификации WHO 5th edition, 2019) (p=0,001/p=0,018), промежуточным морфологическим типом по классификации P. Lauren (p=0,027/p=0,005) и отсутствием перстневидных клеток (p=0,001/p=0,010). Окрашивание обоими используемыми клонами не было ассоциировано с полом и возрастом пациентов, размером и локализацией опухоли, степенью ее дифференцировки, наличием или отсутствием эмболов в просветах кровеносных и лимфатических сосудов, наличием пораженных лимфатических узлов и отдаленных метастазов, а также клинической стадией (р&gt;0,05). Наибольшая доля PD-L1 положительных случаев при исследовании клонов SP263/SP142 обнаружена в опухолях тубулярного типа (75,6%/84,6%) по классификации WHO 5th edition, 2019 год, промежуточного типа (60,0%/68,0%) по P. Lauren, 2 типа (65,4%/68,0%) по R. Bormann и при отсутствии перстневидных клеток (70,7%/76,9%). Заключение. Статистически значимыми клиникоморфологическими параметрами рака желудка, где выявлена достоверная взаимосвязь между ними и экспрессией PD-L1 клонов SP263 и SP142, являются: 2-й тип макроскопической формы по R. Bormann (p=0,003/p=0,003), тубулярный морфологический тип по классификации WHO 5th edition, 2019) (p=0,001/p=0,018), промежуточный тип по P. Lauren (p=0,027/p=0,005) и отсутствие перстневидных клеток (p=0,001/p=0,010).</p></abstract><trans-abstract xml:lang="en"><p>The aim is to study the relationship of PD-L1 status of SP142 and SP263 clones in gastric cancer with its clinical and morphological parameters. Material and methods. Surgical material obtained from 131 patients with a confirmed diagnosis of stomach cancer. Antibodies to PD-L1 SP263 were stained 127 cases, antibodies to PD-L1 SP142 – 126 cases. Reactions with PD-L1 were performed using the Ventana BenchMark Ultra device (Roche Ventana, USA) according to the protocols recommended by the manufacturer of primary antibodies. The results of immunohistochemical staining were compared with the clinical and morphological characteristics of gastric cancer using statistical analysis. Results. The positive PD-L1 status detected by clones SP263 and SP142 is significantly associated with type 2 macroscopic form according to the R. Bormann classification (p=0,003/p=0,003), tubular morphological type according to the WHO 5th edition, 2019 classification (p=0,001/p=0,018), intermediate morphological type according to the classification of P. Lauren (p=0,027/p=0,005) and the absence of signet ring cells (p=0,001/p=0,010). Staining with both clones used was not associated with the gender and age of patients, the size and localization of the tumor, the degree of its differentiation, the presence or absence of emboli in the lumen of blood and lymph vessels, the presence of affected lymph nodes and distant metastases, as well as the clinical stage (p&gt;0,05). The largest proportion of PD-L1 positive cases in the study of SP263/SP142 clones was found in tubular type tumors (75,6%/84,6%) according to the WHO 5th edition, 2019 classification, intermediate type (60,0%/68,0%) according to P. Lauren, type 2 (65,4%/68,0%) according to R. Bormann and in the absence of signet ring cells (70,7%/76,9%). Conclusion. Statistically significant clinical and morphological parameters of gastric cancer, where a reliable relationship between them and the expression of PD-L1 clones SP263 and SP142 was revealed, are: type 2 macroscopic form according to R. Bormann (p=0,003/p=0,003), tubular morphological type according to the classification of WHO 5th edition, 2019) (p=0,001/p=0,018), intermediate type according to P. Lauren (p=0,027/p=0,005) and the absence of signet ring cells (p=0,001/p=0,010).</p></trans-abstract><kwd-group xml:lang="ru"><kwd>рак желудка</kwd><kwd>PD1-статус</kwd><kwd>PD-L1-статус</kwd><kwd>клон SP263</kwd><kwd>клон SP142</kwd><kwd>клиникоморфологические характеристики</kwd></kwd-group><kwd-group xml:lang="en"><kwd>gastric cancer</kwd><kwd>PD1 status</kwd><kwd>PD-L1 status</kwd><kwd>clone SP263</kwd><kwd>clone SP142</kwd><kwd>clinical and morphological characteristics</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Данилова Н.В., Сотникова Т.Н., Калинин Д.В., Олейникова Н.А., Чайка А.В., Хомяков В.М., и др. Экспрессия PD-L1 в EBV-ассоциированном раке желудка. Архив патологии. 2022;84(4):5– 12. doi: 10.17116/patol2022840415</mixed-citation><mixed-citation xml:lang="en">Danilova N, Sotnikova TN, Kalinin DV, Oleynikova NA, Chayka AV, Khomyakov VM, et al. PD-L1 expression in EBV-associated gastric carcinomas. Arkhiv patologii. 2022 Jan 1;84(4):5– 12 (In Russ.). doi: 10.17116/patol2022840415</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a Cancer Journal for Clinicians. 2018 Sep 12;68(6):394–424. doi: 10.3322/caac.21492</mixed-citation><mixed-citation xml:lang="en">Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a Cancer Journal for Clinicians. 2018 Sep 12;68(6):394–424. doi: 10.3322/caac.21492</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Chen L, Wang L, Li X, Zhang G, Li Z, Wang Y. Clinic-Pathological Characteristics and Prognostic Value of PD-L1 and HER2 in Gastric Cancer. DNA and Cell Biology. 2021 Feb 1;40(2):405–13. doi: 10.1089/dna.2020.6232</mixed-citation><mixed-citation xml:lang="en">Chen L, Wang L, Li X, Zhang G, Li Z, Wang Y. Clinic-Pathological Characteristics and Prognostic Value of PD-L1 and HER2 in Gastric Cancer. DNA and Cell Biology. 2021 Feb 1;40(2):405–13. doi: 10.1089/dna.2020.6232</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Eto S, Yoshikawa K, Nishi M, Higashijima J, Tokunaga T, Nakao T, et al. Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection. Gastric Cancer. 2015 Jul 26;19(2):466– 71. doi: 10.1007/s10120-015-0519-7</mixed-citation><mixed-citation xml:lang="en">Eto S, Yoshikawa K, Nishi M, Higashijima J, Tokunaga T, Nakao T, et al. Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection. Gastric Cancer. 2015 Jul 26;19(2):466– 71. doi: 10.1007/s10120-015-0519-7</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Ghosh C, Luong G, Sun Y. A snapshot of the PD1/PD-L1 pathway. Journal of Cancer. 2021;12(9):2735–46. doi: 10.7150/jca.57334</mixed-citation><mixed-citation xml:lang="en">Ghosh C, Luong G, Sun Y. A snapshot of the PD1/PD-L1 pathway. Journal of Cancer. 2021;12(9):2735–46. doi: 10.7150/jca.57334</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Gu L, Chen M, Guo D, Zhu H, Zhang W, Pan J, et al. PD-L1 and gastric cancer prognosis: A systematic review and meta-analysis. Katoh M, editor. PLOS ONE [Internet]. 2017 Aug 10;12(8):e0182692. doi: 10.1371/journal.pone.0182692</mixed-citation><mixed-citation xml:lang="en">Gu L, Chen M, Guo D, Zhu H, Zhang W, Pan J, et al. PD-L1 and gastric cancer prognosis: A systematic review and meta-analysis. Katoh M, editor. PLOS ONE [Internet]. 2017 Aug 10;12(8):e0182692. doi: 10.1371/journal.pone.0182692</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet (London, England) [Internet]. 2016;387(10027):1540–50. doi: 10.1016/S0140-6736(15)01281-7</mixed-citation><mixed-citation xml:lang="en">Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet (London, England) [Internet]. 2016;387(10027):1540–50. doi: 10.1016/S0140-6736(15)01281-7</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Kawazoe A, Shitara K, Kuboki Y, Bando H, Kojima T, Yoshino T, et al. Clinicopathological features of 22C3 PD-L1 expression with mismatch repair, Epstein–Barr virus status, and cancer genome alterations in metastatic gastric cancer. Gastric Cancer. 2018 Jun 1;22(1):69–76. doi: 10.1007/s10120-018-0843-9</mixed-citation><mixed-citation xml:lang="en">Kawazoe A, Shitara K, Kuboki Y, Bando H, Kojima T, Yoshino T, et al. Clinicopathological features of 22C3 PD-L1 expression with mismatch repair, Epstein–Barr virus status, and cancer genome alterations in metastatic gastric cancer. Gastric Cancer. 2018 Jun 1;22(1):69–76. doi: 10.1007/s10120-018-0843-9</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Kim JW, Nam KH, Ahn SH, Park DJ, Kim HH, Kim SH, et al. Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer. Gastric Cancer. 2014 Nov 26;19(1):42–52. doi: 10.1007/s10120-014-0440-5</mixed-citation><mixed-citation xml:lang="en">Kim JW, Nam KH, Ahn SH, Park DJ, Kim HH, Kim SH, et al. Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer. Gastric Cancer. 2014 Nov 26;19(1):42–52. doi: 10.1007/s10120-014-0440-5</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Kim SW, Jeong G, Ryu MH, Park YS. Comparison of PD-L1 immunohistochemical assays in advanced gastric adenocarcinomas using endoscopic biopsy and paired resected specimens. Pathology. 2021 Aug;53(5):586–94. doi: 10.1016/j.pathol.2020.10.015</mixed-citation><mixed-citation xml:lang="en">Kim SW, Jeong G, Ryu MH, Park YS. Comparison of PD-L1 immunohistochemical assays in advanced gastric adenocarcinomas using endoscopic biopsy and paired resected specimens. Pathology. 2021 Aug;53(5):586–94. doi: 10.1016/j.pathol.2020.10.015</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Kwok G, Yau TCC, Chiu JW, Tse E, Kwong YL. Pembrolizumab (Keytruda). Human Vaccines &amp; Immunotherapeutics. 2016 Jul 11;12(11):2777–89. doi: 10.1080/21645515.2016.1199310</mixed-citation><mixed-citation xml:lang="en">Kwok G, Yau TCC, Chiu JW, Tse E, Kwong YL. Pembrolizumab (Keytruda). Human Vaccines &amp; Immunotherapeutics. 2016 Jul 11;12(11):2777–89. doi: 10.1080/21645515.2016.1199310</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Liu X, Min Gew Choi, Kim K, Kim K, Se Hoon Park, Răzvan Cristescu, et al. High PD-L1 expression in gastric cancer (GC) patients and correlation with molecular features. Pathology - Research and Practice. 2020 Apr 1;216(4):152881–1. doi: 10.1016/j.prp.2020.152881</mixed-citation><mixed-citation xml:lang="en">Liu X, Min Gew Choi, Kim K, Kim K, Se Hoon Park, Răzvan Cristescu, et al. High PD-L1 expression in gastric cancer (GC) patients and correlation with molecular features. Pathology - Research and Practice. 2020 Apr 1;216(4):152881–1. doi: 10.1016/j.prp.2020.152881</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Ma J, Li J, Qian M, Han W, Tian M, Li Z, et al. PDL1 expression and the prognostic significance in gastric cancer: a retrospective comparison of three PD-L1 antibody clones (SP142, 28–8 and E1L3N). Diagnostic Pathology. 2018 Nov 21;13(1):91. doi: 10.1186/s13000-018-0766-0</mixed-citation><mixed-citation xml:lang="en">Ma J, Li J, Qian M, Han W, Tian M, Li Z, et al. PDL1 expression and the prognostic significance in gastric cancer: a retrospective comparison of three PD-L1 antibody clones (SP142, 28–8 and E1L3N). Diagnostic Pathology. 2018 Nov 21;13(1):91. doi: 10.1186/s13000-018-0766-0</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–SmallCell Lung Cancer. New England Journal of Medicine. 2016 Nov 10;375(19):1823–33. doi: 10.1056/NEJMoa1606774</mixed-citation><mixed-citation xml:lang="en">Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–SmallCell Lung Cancer. New England Journal of Medicine. 2016 Nov 10;375(19):1823–33. doi: 10.1056/NEJMoa1606774</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJM, Robert L, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature [Internet]. 2014;515(7528):568–71. doi: 10.1038/nature13954</mixed-citation><mixed-citation xml:lang="en">Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJM, Robert L, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature [Internet]. 2014;515(7528):568–71. doi: 10.1038/nature13954</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Yoshida T, Ogura G, Tanabe M, Hayashi T, Ohbayashi C, Azuma M, et al. Clinicopathological features of PD-L1 protein expression, EBV positivity, and MSI status in patients with advanced gastric and esophagogastric junction adenocarcinoma in Japan. Cancer Biology &amp; Therapy. 2022 Feb 27;23(1):191–200. doi: 10.1080/15384047.2022.2038002</mixed-citation><mixed-citation xml:lang="en">Yoshida T, Ogura G, Tanabe M, Hayashi T, Ohbayashi C, Azuma M, et al. Clinicopathological features of PD-L1 protein expression, EBV positivity, and MSI status in patients with advanced gastric and esophagogastric junction adenocarcinoma in Japan. Cancer Biology &amp; Therapy. 2022 Feb 27;23(1):191–200. doi: 10.1080/15384047.2022.2038002</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang M, Dong Y, Liu H, Wang Y, Zhao S, Xuan Q, et al. The clinicopathological and prognostic significance of PD-L1 expression in gastric cancer: a meta-analysis of 10 studies with 1,901 patients. Scientific Reports. 2016 Nov 28;6(1):37933. doi: 10.1038/srep37933</mixed-citation><mixed-citation xml:lang="en">Zhang M, Dong Y, Liu H, Wang Y, Zhao S, Xuan Q, et al. The clinicopathological and prognostic significance of PD-L1 expression in gastric cancer: a meta-analysis of 10 studies with 1,901 patients. Scientific Reports. 2016 Nov 28;6(1):37933. doi: 10.1038/srep37933</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Zhou YJ, Li G, Wang J, Liu M, Wang Z, Song Y, et al. PD-L1: expression regulation. Blood Science. 2023 Jan 13;5(2):77–91. doi: 10.1097/BS9.0000000000000149</mixed-citation><mixed-citation xml:lang="en">Zhou YJ, Li G, Wang J, Liu M, Wang Z, Song Y, et al. PD-L1: expression regulation. Blood Science. 2023 Jan 13;5(2):77–91. doi: 10.1097/BS9.0000000000000149</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
