<?xml version="1.0" encoding="utf-8"?>
<article xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" dtd-version="1.4" article-type="research-article">
  <front>
    <journal-meta>
      <journal-id journal-id-type="issn">2226-5988</journal-id>
      <journal-id journal-id-type="eissn">2686-6749</journal-id>
      <journal-title-group>
        <journal-title xml:lang="ru">Клиническая и экспериментальная морфология</journal-title>
        <journal-title xml:lang="en">Clinical and Experimental Morphology</journal-title>
      </journal-title-group>
      <publisher>
        <publisher-name>ООО "Группа МДВ"</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="doi">10.31088/cem2023.12.2.25-35</article-id>
      <title-group>
        <article-title xml:lang="ru">Особенности распространения опухоли по воздушным пространствам у пациентов с немелкоклеточным раком легкого</article-title>
        <trans-title-group xml:lang="en">
          <trans-title>Features of tumor spread through the air spaces in patients with non-small cell lung carcinoma</trans-title>
        </trans-title-group>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author" corresp="yes">
          <name name-style="eastern">
            <surname>Завьялова</surname>
            <given-names>Марина Викторовна</given-names>
          </name>
          <name-alternatives>
            <name name-style="eastern" xml:lang="ru">
              <surname>Завьялова</surname>
              <given-names>Марина Викторовна</given-names>
            </name>
            <name name-style="western" xml:lang="en">
              <surname>Zavyalova</surname>
              <given-names>Marina V.</given-names>
            </name>
          </name-alternatives>
          <email>zavyalovamv@mail.ru</email>
          <contrib-id contrib-id-type="orcid">0000-0001-9429-9813</contrib-id>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name name-style="eastern">
            <surname>Лоос</surname>
            <given-names>Дмитрий Максимович</given-names>
          </name>
          <name-alternatives>
            <name name-style="eastern" xml:lang="ru">
              <surname>Лоос</surname>
              <given-names>Дмитрий Максимович</given-names>
            </name>
            <name name-style="western" xml:lang="en">
              <surname>Loos</surname>
              <given-names>Dmitry M.</given-names>
            </name>
          </name-alternatives>
          <email>cem.journal@mail.ru</email>
          <contrib-id contrib-id-type="orcid">0000-0002-4098-6076</contrib-id>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name name-style="eastern">
            <surname>Письменный</surname>
            <given-names>Дмитрий Сергеевич</given-names>
          </name>
          <name-alternatives>
            <name name-style="eastern" xml:lang="ru">
              <surname>Письменный</surname>
              <given-names>Дмитрий Сергеевич</given-names>
            </name>
            <name name-style="western" xml:lang="en">
              <surname>Pismenny</surname>
              <given-names>Dmitry S.</given-names>
            </name>
          </name-alternatives>
          <email>cem.journal@mail.ru</email>
          <contrib-id contrib-id-type="orcid">0000-0001-8973-8439</contrib-id>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name name-style="eastern">
            <surname>Дурова</surname>
            <given-names>Анастасия Алексеевна</given-names>
          </name>
          <name-alternatives>
            <name name-style="eastern" xml:lang="ru">
              <surname>Дурова</surname>
              <given-names>Анастасия Алексеевна</given-names>
            </name>
            <name name-style="western" xml:lang="en">
              <surname>Durova</surname>
              <given-names>Anastasia A.</given-names>
            </name>
          </name-alternatives>
          <email>cem.journal@mail.ru</email>
          <contrib-id contrib-id-type="orcid">0000-0003-3225-2440</contrib-id>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name name-style="eastern">
            <surname>Андрюхова</surname>
            <given-names>Елена Сергеевна</given-names>
          </name>
          <name-alternatives>
            <name name-style="eastern" xml:lang="ru">
              <surname>Андрюхова</surname>
              <given-names>Елена Сергеевна</given-names>
            </name>
            <name name-style="western" xml:lang="en">
              <surname>Andryukhova</surname>
              <given-names>Elena S.</given-names>
            </name>
          </name-alternatives>
          <email>cem.journal@mail.ru</email>
          <contrib-id contrib-id-type="orcid">0000-0003-0909-9206</contrib-id>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name name-style="eastern">
            <surname>Родионов</surname>
            <given-names>Евгений Олегович</given-names>
          </name>
          <name-alternatives>
            <name name-style="eastern" xml:lang="ru">
              <surname>Родионов</surname>
              <given-names>Евгений Олегович</given-names>
            </name>
            <name name-style="western" xml:lang="en">
              <surname>Rodionov</surname>
              <given-names>Evgeniy O.</given-names>
            </name>
          </name-alternatives>
          <email>cem.journal@mail.ru</email>
          <contrib-id contrib-id-type="orcid">0000-0003-4980-8986</contrib-id>
          <xref ref-type="aff" rid="aff3"/>
        </contrib>
        <contrib contrib-type="author">
          <name name-style="eastern">
            <surname>Миллер</surname>
            <given-names>Сергей Викторович</given-names>
          </name>
          <name-alternatives>
            <name name-style="eastern" xml:lang="ru">
              <surname>Миллер</surname>
              <given-names>Сергей Викторович</given-names>
            </name>
            <name name-style="western" xml:lang="en">
              <surname>Miller</surname>
              <given-names>Sergey V.</given-names>
            </name>
          </name-alternatives>
          <email>cem.journal@mail.ru</email>
          <contrib-id contrib-id-type="orcid">0000-0002-5365-9840</contrib-id>
          <xref ref-type="aff" rid="aff3"/>
        </contrib>
        <contrib contrib-type="author">
          <name name-style="eastern">
            <surname>Тузиков</surname>
            <given-names>Сергей Александрович</given-names>
          </name>
          <name-alternatives>
            <name name-style="eastern" xml:lang="ru">
              <surname>Тузиков</surname>
              <given-names>Сергей Александрович</given-names>
            </name>
            <name name-style="western" xml:lang="en">
              <surname>Tuzikov</surname>
              <given-names>Sergei A.</given-names>
            </name>
          </name-alternatives>
          <email>cem.journal@mail.ru</email>
          <contrib-id contrib-id-type="orcid">0000-0002-0884-1838</contrib-id>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name name-style="eastern">
            <surname>Таширева</surname>
            <given-names>Любовь Александровна</given-names>
          </name>
          <name-alternatives>
            <name name-style="eastern" xml:lang="ru">
              <surname>Таширева</surname>
              <given-names>Любовь Александровна</given-names>
            </name>
            <name name-style="western" xml:lang="en">
              <surname>Tashireva</surname>
              <given-names>Lyubov A.</given-names>
            </name>
          </name-alternatives>
          <email>cem.journal@mail.ru</email>
          <contrib-id contrib-id-type="orcid">0000-0003-2061-8417</contrib-id>
          <xref ref-type="aff" rid="aff3"/>
        </contrib>
        <contrib contrib-type="author">
          <name name-style="eastern">
            <surname>Панкова</surname>
            <given-names>Ольга Владимировна</given-names>
          </name>
          <name-alternatives>
            <name name-style="eastern" xml:lang="ru">
              <surname>Панкова</surname>
              <given-names>Ольга Владимировна</given-names>
            </name>
            <name name-style="western" xml:lang="en">
              <surname>Pankova</surname>
              <given-names>Olga V.</given-names>
            </name>
          </name-alternatives>
          <email>cem.journal@mail.ru</email>
          <contrib-id contrib-id-type="orcid">0000-0002-5510-1808</contrib-id>
          <xref ref-type="aff" rid="aff3"/>
        </contrib>
        <contrib contrib-type="author">
          <name name-style="eastern">
            <surname>Перельмутер</surname>
            <given-names>Владимир Михайлович</given-names>
          </name>
          <name-alternatives>
            <name name-style="eastern" xml:lang="ru">
              <surname>Перельмутер</surname>
              <given-names>Владимир Михайлович</given-names>
            </name>
            <name name-style="western" xml:lang="en">
              <surname>Perelmuter</surname>
              <given-names>Vladimir M.</given-names>
            </name>
          </name-alternatives>
          <email>cem.journal@mail.ru</email>
          <contrib-id contrib-id-type="orcid">0000-0002-7633-9620</contrib-id>
          <xref ref-type="aff" rid="aff3"/>
        </contrib>
        <aff-alternatives id="aff1">
          <aff>
            <institution xml:lang="ru">ФГБНУ Томский национальный исследовательский медицинский центр Российской академии наук, Научно-исследовательский институт онкологии; ФГБОУ ВО Сибирский государственный медицинский университет Минздрава России (Томск, Россия)</institution>
          </aff>
          <aff>
            <institution xml:lang="en">Tomsk National Research Medical Center of the Russian Academy of Sciences, Cancer Research Institute; Siberian State Medical University (Tomsk, Russia)</institution>
          </aff>
        </aff-alternatives>
        <aff-alternatives id="aff2">
          <aff>
            <institution xml:lang="ru">ФГБОУ ВО Сибирский государственный медицинский университет Минздрава России (Томск, Россия)</institution>
          </aff>
          <aff>
            <institution xml:lang="en">Siberian State Medical University (Tomsk, Russia)</institution>
          </aff>
        </aff-alternatives>
        <aff-alternatives id="aff3">
          <aff>
            <institution xml:lang="ru">ФГБНУ Томский национальный исследовательский медицинский центр Российской академии наук, Научно-исследовательский институт онкологии (Томск, Россия)</institution>
          </aff>
          <aff>
            <institution xml:lang="en">Tomsk National Research Medical Center of the Russian Academy of Sciences, Cancer Research Institute (Tomsk, Russia)</institution>
          </aff>
        </aff-alternatives>
      </contrib-group>
      <pub-date pub-type="epub" iso-8601-date="2023-06-19">
        <day>19</day>
        <month>06</month>
        <year>2023</year>
      </pub-date>
      <pub-date date-type="collection">
        <year>2023</year>
      </pub-date>
      <volume>12</volume>
      <issue>2</issue>
      <fpage>25</fpage>
      <lpage>35</lpage>
      <history>
        <date date-type="received" iso-8601-date="2022-05-17">
          <day>17</day>
          <month>05</month>
          <year>2022</year>
        </date>
        <date date-type="accepted" iso-8601-date="2022-12-12">
          <day>12</day>
          <month>12</month>
          <year>2022</year>
        </date>
        <date date-type="rev-recd" iso-8601-date="2022-09-16">
          <day>16</day>
          <month>09</month>
          <year>2022</year>
        </date>
      </history>
      <abstract xml:lang="ru">
        <p>Введение. В настоящее время молекулярные механизмы, лежащие в основе развития STAS – маркера неблагоприятного исхода рака легких, остаются до конца не изученными. Не исключено, что развитие STAS может быть ассоциировано с маркерами высокого риска гематогенного метастазирования и рецидивирования – изменениями бронхиального эпителия. Цель исследования – изучить особенности STAS у пациентов с разными морфологическими изменениями бронхиального эпителия бронхов. Материалы и методы. Исследовали операционный материал от 90 пациентов с немелкоклеточным раком легкого (НМРЛ), проходивших лечение в торакоабдоминальном отделении НИИ онкологии Томского НИМЦ в период с 2009 по 2017 год. Все пациенты получали комбинированное лечение. Анализировали истории болезни и амбулаторные карты пациентов. Распространенность заболевания определялась согласно Международной классификации по системе TNM 2017 года. Проводка материала и изготовление гистологических препаратов осуществлялись по стандартной методике. Гистологический тип рака определялся согласно классификации ВОЗ 2015 года. В исследование были включены только случаи с НМРЛ, а именно с плоскоклеточным раком (n=50) или аденокарциномой (n=40). В лимфатических узлах оценивали наличие метастатического поражения, подсчитывали число лимфоузлов с метастазами. В слизистой оболочке бронхов, располагающихся на 3–4 см от границы опухоли, оценивали наличие изменений бронхиального эпителия. Учитывали информацию о наличии, сроках и локализации гематогенных метастазов и рецидивов. Применялись методы описательной статистики. Обсуждались результаты с достоверностью различий при р&lt;0,05. Результаты. Проведенное исследование позволило выявить ряд закономерностей, которые могут дополнить представления о патогенезе такой формы прогрессии новообразования, актуальной для рака легкого, как распространение опухоли по воздушным пространствам. Заключение. Исходя из полученных данных, обнаружение STAS предлагается рассматривать как неблагоприятный прогностический признак, связанный с риском локорегионарного метастазирования.</p>
      </abstract>
      <trans-abstract xml:lang="en">
        <p>Introduction. To date, the molecular mechanisms underlying the development of STAS remain poorly understood. The development of STAS – a marker of an unfavorable outcome of lung cancer – is likely to be associated with markers of a high risk of hematogenous metastasis and recurrence, i.e., changes in the bronchial epithelium.The paper aimed to study the features of STAS in patients with different morphological changes in the bronchial epithelium. Materials and methods. We studied surgical material from 90 patients with non-small cell lung cancer who received combined treatment in the thoracoabdominal department of the Research Institute of Oncology of the Tomsk National Research Medical Center between 2009 and 2017. Case histories and outpatient cards of patients were analyzed. We determined the prevalence of the disease according to the international classification using the TNM staging system (2017). We used the standard method to post the material and manufacture histological preparations. The 2015 WHO classification was used to determine the histological type of cancer. The study included only cases with non-small cell lung carcinoma, namely squamous cell carcinoma (n=50) or adenocarcinoma (n=40). In the lymph nodes, we assessed the presence of metastatic lesions and counted the number of lymph nodes with metastases. In the bronchial mucosa located 3–4 cm from the border of the tumor, we assessed the presence of changes in the bronchial epithelium. The information about the presence, timing, and location of hematogenous metastases and relapses was taken into account. We used descriptive statistics; the results were discussed with the statistically significant difference at p&amp;lt;0.05. Results. We identified a number of patterns that could complement the understanding of SPAS pathogenesis, a form of tumor progression relevant for lung cancer. Conclusion. We propose to consider the detection of STAS as an unfavorable prognostic sign associated with the risk of locoregional metastasis.  Keywords: STAS, non-small cell lung cancer, regenerative hyperplasia of the bronchial epithelium, metaplasia of the bronchial epithelium, metastasis</p>
      </trans-abstract>
      <kwd-group xml:lang="ru">
        <title>Ключевые слова</title>
        <kwd>STAS</kwd>
        <kwd>немелкоклеточный рак легкого</kwd>
        <kwd>регенераторная гиперплазия бронхиального эпителия</kwd>
        <kwd>метаплазия бронхиального эпителия</kwd>
        <kwd>метастазирование</kwd>
      </kwd-group>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>STAS</kwd>
        <kwd>non-small cell lung cancer</kwd>
        <kwd>regenerative hyperplasia of the bronchial epithelium</kwd>
        <kwd>metaplasia of the bronchial epithelium</kwd>
        <kwd>metastasis</kwd>
      </kwd-group>
      <funding-group>
        <funding-statement xml:lang="ru">Исследование выполнено в рамках государственного бюджетного финансирования.</funding-statement>
        <funding-statement xml:lang="en">The study was carried out within the framework of state budget funding.</funding-statement>
      </funding-group>
    </article-meta>
  </front>
  <body/>
  <back>
    <ref-list>
      <ref id="ref1">
        <label>1</label>
        <mixed-citation xml:lang="ru">Kadota K, Nitadori JI, Sima CS, Ujiie H, Rizk NP, Jones DR et al. Tumor spread through air spaces is an important pattern of invasion and impacts the frequency and location of recurrences after limited resection for small stage I lung adenocarcinomas. J Thorac Oncol. 2015;10(5):806–14. DOI: 10.1097/JTO.0000000000000486.</mixed-citation>
      </ref>
      <ref id="ref2">
        <label>2</label>
        <mixed-citation xml:lang="ru">Kadota K, Kushida Y, Katsuki N, Ishikawa R, Ibuki E, Motoyama M et al. Tumor spread through air spaces is an independent predictor of recurrence-free survival in patients with resected lung squamous cell carcinoma. Am J Surg Pathol. 2017;41(8):1077–86. DOI: 10.1097/PAS.0000000000000872.</mixed-citation>
      </ref>
      <ref id="ref3">
        <label>3</label>
        <mixed-citation xml:lang="ru">Lu S, Tan KS, Kadota K, Eguchi T, Bains S, Rekhtman N et al. Spread through Air Spaces (STAS) is an independent predictor of recurrence and lung cancer-specific death in squamous cell carcinoma. J Thorac Oncol. 2017;12(2):223–34. DOI: 10.1016/j.jtho.2016.09.129.</mixed-citation>
      </ref>
      <ref id="ref4">
        <label>4</label>
        <mixed-citation xml:lang="ru">Yanagawa N, Shiono S, Endo M, Ogata SY. Tumor spread through air spaces is a useful predictor of recurrence and prognosis in stage I lung squamous cell carcinoma, but not in stage II and III. Lung Cancer. 2018;120:14–21. DOI: 10.1016/j.lungcan.2018.03.018.</mixed-citation>
      </ref>
      <ref id="ref5">
        <label>5</label>
        <mixed-citation xml:lang="ru">Han YB, Kim H, Mino-Kenudson M, Cho S, Kwon HJ, Lee KR et al. Tumor spread through air spaces (STAS): Prognostic significance of grading in non-small cell lung cancer. Mod Pathol. 2021;34(3):549–61. DOI: 10.1038/s41379-020-00709-2.</mixed-citation>
      </ref>
      <ref id="ref6">
        <label>6</label>
        <mixed-citation xml:lang="ru">Warth A. Spread through air spaces (STAS): A comprehensive update. Transl Lung Cancer Res. 2017;6(5):501–7. DOI: 10.21037/tlcr.2017.06.08.</mixed-citation>
      </ref>
      <ref id="ref7">
        <label>7</label>
        <mixed-citation xml:lang="ru">Mino-Kenudson M. Significance of tumor spread through air spaces (STAS) in lung cancer from the pathologist perspective. Transl Lung Cancer Res. 2020;9(3):847–59. DOI: 10.21037/tlcr.2020.01.06.</mixed-citation>
      </ref>
      <ref id="ref8">
        <label>8</label>
        <mixed-citation xml:lang="ru">Song T, Jiang L, Zhuo Z, Luo J, Alai G, Shen X et al. Impacts of thoracoscopic surgery and high grade histologic subtypes on spread through air spaces in small stage I lung adenocarcinomas. J Cancer Res Clin Oncol. 2019; 145(9):2375–82. DOI: 10.1007/s00432-019-02972-6.</mixed-citation>
      </ref>
      <ref id="ref9">
        <label>9</label>
        <mixed-citation xml:lang="ru">Jia M, Yu S, Yu J, Li Y, Gao H, Sun PL. Comprehensive analysis of spread through air spaces in lung adenocarcinoma and squamous cell carcinoma using the 8th edition AJCC/UICC staging system. BMC Cancer. 2020;20(1):705. DOI: 10.1186/s12885-020-07200-w.</mixed-citation>
      </ref>
      <ref id="ref10">
        <label>10</label>
        <mixed-citation xml:lang="ru">Tsoukalas N, Aravantinou-Fatorou E, Tolia M, Giaginis C, Galanopoulos M, Kiakou M et al. Epithelial-mesenchymal transition in non small-cell lung cancer. Anticancer Res. 2017;37(4):1773–8. DOI: 10.21873/anticanres.11510.</mixed-citation>
      </ref>
      <ref id="ref11">
        <label>11</label>
        <mixed-citation xml:lang="ru">Yagi Y, Aly RG, Tabata K, Barlas A, Rekhtman N, Eguchi T et al. Three-Dimensional histologic, immunohistochemical, and multiplex immunofluorescence analyses of dynamic vessel co-option of spread through air spaces in lung adenocarcinoma. J Thorac Oncol. 2020;15(4):589–600. DOI: 10.1016/j.jtho.2019.12.112.</mixed-citation>
      </ref>
      <ref id="ref12">
        <label>12</label>
        <mixed-citation xml:lang="ru">Kerr KM, Popper HH. The differential diagnosis of pulmonary pre-invasive lesions. In: W Timens, HH Popper (eds.). Pathology of the Lung. European Respiratory Society Monograph. 2007. V. 39. P. 37–62. DOI: 10.1183/1025448x.ERM3907.</mixed-citation>
      </ref>
      <ref id="ref13">
        <label>13</label>
        <mixed-citation xml:lang="ru">Dacic S. Pulmonary preneoplasia. Arch Pathol Lab Med. 2008;132(7):1073–8. DOI: 10.5858/2008-132-1073-PP.</mixed-citation>
      </ref>
      <ref id="ref14">
        <label>14</label>
        <mixed-citation xml:lang="ru">Lantuéjoul S, Salameire D, Salon C, Brambilla E. Pulmonary preneoplasia-sequential molecular carcinogenetic events. Histopathology. 2009;54(1):43–54. DOI: 10.1111/j.1365-2559.2008.03182x.</mixed-citation>
      </ref>
      <ref id="ref15">
        <label>15</label>
        <mixed-citation xml:lang="ru">Pankova OV, Tashireva LA, Rodionov EO, Miller SV, Tuzikov SA, Pismenny DS et al. Premalignant changes in the bronchial epithelium are prognostic factors of distant metastasis in non-small cell lung cancer patients. Front Oncol. 2021;11:771802. DOI: 10.3389/fonc.2021.771802.</mixed-citation>
      </ref>
      <ref id="ref16">
        <label>16</label>
        <mixed-citation xml:lang="ru">Pankova OV, Denisov EV, Ponomaryova AA, Gerashchenko TS, Tuzikov SA, Perelmuter VM. Recurrence of squamous cell lung carcinoma is associated with the co-presence of reactive lesions in tumor-adjacent bronchial epithelium. Tumour Biol. 2016;37(3):3599–607. DOI: 10.1007/s13277-015-4196-2.</mixed-citation>
      </ref>
      <ref id="ref17">
        <label>17</label>
        <mixed-citation xml:lang="ru">MB Amin, SB Edge, FL Greene, DR Byrd, RK Brookland, MK Washington et al (eds.). AJCC Cancer Staging Manual. 8th ed. Springer International Publishing, Cham: American College of Surgeons, 2017. 1049 p.</mixed-citation>
      </ref>
      <ref id="ref18">
        <label>18</label>
        <mixed-citation xml:lang="ru">Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JHM, Beasley MB et al. The 2015 World Health Organization Classification of Lung Tumors: Impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 2015;10(9):1243–60. DOI: 10.1097/JTO.0000000000000630.</mixed-citation>
      </ref>
      <ref id="ref19">
        <label>19</label>
        <mixed-citation xml:lang="ru">Warth A, Muley T, Kossakowski CA, Goeppert B, Schirmacher P, Dienemann H et al. Prognostic impact of intra-alveolar tumor spread in pulmonary adenocarcinoma. Am J Surg Pathol. 2015;39(6):793–801. DOI: 10.1097/PAS.0000000000000409.</mixed-citation>
      </ref>
    </ref-list>
  </back>
</article>
