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<article 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" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Kazan medical journal</journal-id><journal-title-group><journal-title xml:lang="en">Kazan medical journal</journal-title><trans-title-group xml:lang="ru"><trans-title>Казанский медицинский журнал</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0368-4814</issn><issn publication-format="electronic">2587-9359</issn><publisher><publisher-name xml:lang="en">Eco-Vector</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">646632</article-id><article-id pub-id-type="doi">10.17816/KMJ646632</article-id><article-id pub-id-type="edn">CEUIEC</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Theoretical and clinical medicine</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Теоретическая и клиническая медицина</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Effectiveness of adding molecular-genetic testing to liquid-based papanicolaou cytology for detecting endometrial cancer in women with comorbidities</article-title><trans-title-group xml:lang="ru"><trans-title>Эффективность дополнительного молекулярно-генетического тестирования при жидкостной цитологии по Папаниколау для выявления рака тела матки у женщин с коморбидной патологией</trans-title></trans-title-group><trans-title-group xml:lang="zh"><trans-title>巴氏液细胞学中额外分子基因检测对合并症病理妇女子宫体癌检测的有效性</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0005-8204-705X</contrib-id><contrib-id contrib-id-type="spin">5882-7437</contrib-id><name-alternatives><name xml:lang="en"><surname>Grafskaya</surname><given-names>Mariya Yu.</given-names></name><name xml:lang="ru"><surname>Графская</surname><given-names>Мария Юрьевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Cand. Sci. (Medicine), Assistant Professor, Doctoral Student</p></bio><bio xml:lang="ru"><p>канд. мед. наук, доцент, докторант</p></bio><email>mariagrafskaja@ya.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1084-5176</contrib-id><contrib-id contrib-id-type="spin">6610-7824</contrib-id><name-alternatives><name xml:lang="en"><surname>Verenikina</surname><given-names>Ekaterina V.</given-names></name><name xml:lang="ru"><surname>Вереникина</surname><given-names>Екатерина Владимировна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Dr. Sci. (Medicine), Head, Depart. of Oncogynecology</p></bio><bio xml:lang="ru"><p>д-р мед. наук, заведующая, отд. онкогинекологии</p></bio><email>ekat.veren@yandex.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3545-9359</contrib-id><contrib-id contrib-id-type="spin">4014-8502</contrib-id><name-alternatives><name xml:lang="en"><surname>Demidova</surname><given-names>Alexandra A.</given-names></name><name xml:lang="ru"><surname>Демидова</surname><given-names>Александра Александровна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Dr. Sci. (Medicine), Assistant Professor, research associate, Lab. of Molecular Oncology</p></bio><bio xml:lang="ru"><p>д-р мед. наук, доцент, научный сотрудник, лаб. молекулярной онкологии</p></bio><email>alald@inbox.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0006-7638-3097</contrib-id><name-alternatives><name xml:lang="en"><surname>Ermilova</surname><given-names>Mariya V.</given-names></name><name xml:lang="ru"><surname>Ермилова</surname><given-names>Мария Викторовна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Doctor, Consulting Clinic</p></bio><bio xml:lang="ru"><p>врач, консультативная поликлиника</p></bio><email>mariaermilova@ya.ru</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0008-3611-6749</contrib-id><name-alternatives><name xml:lang="en"><surname>Bova</surname><given-names>Elena V.</given-names></name><name xml:lang="ru"><surname>Бова</surname><given-names>Елена Викторовна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Cand. Sci. (Medicine), Head, Endocrinology Center</p></bio><bio xml:lang="ru"><p>канд. мед. наук, заведующая, эндокринологический центр</p></bio><email>bova_ev@rostgmu.ru</email><xref ref-type="aff" rid="aff3"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">National Medical Research Centre for Oncology</institution></aff><aff><institution xml:lang="ru">Национальный медицинский исследовательский центр онкологии</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">The First Sechenov Moscow State Medical University</institution></aff><aff><institution xml:lang="ru">Первый Московский государственный медицинский университет им. И.М. Сеченова</institution></aff></aff-alternatives><aff-alternatives id="aff3"><aff><institution xml:lang="en">Regional Clinical Hospital No. 2</institution></aff><aff><institution xml:lang="ru">Областная клиническая больница № 2</institution></aff></aff-alternatives><pub-date date-type="preprint" iso-8601-date="2025-07-23" publication-format="electronic"><day>23</day><month>07</month><year>2025</year></pub-date><pub-date date-type="pub" iso-8601-date="2025-08-05" publication-format="electronic"><day>05</day><month>08</month><year>2025</year></pub-date><volume>106</volume><issue>4</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>563</fpage><lpage>569</lpage><history><date date-type="received" iso-8601-date="2025-01-24"><day>24</day><month>01</month><year>2025</year></date><date date-type="accepted" iso-8601-date="2025-04-23"><day>23</day><month>04</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2025, Eco-Vector</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2025, Эко-Вектор</copyright-statement><copyright-statement xml:lang="zh">Copyright ©; 2025,</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="en">Eco-Vector</copyright-holder><copyright-holder xml:lang="ru">Эко-Вектор</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/" start_date="2028-08-05"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://eco-vector.com/for_authors.php#07</ali:license_ref></license></permissions><self-uri xlink:href="https://kazanmedjournal.ru/kazanmedj/article/view/646632">https://kazanmedjournal.ru/kazanmedj/article/view/646632</self-uri><abstract xml:lang="en"><p><bold>BACKGROUND:</bold> Developing an effective screening strategy for women with morbid obesity using accessible and simple biological sampling methods remains critical.</p> <p><bold>AIM:</bold> This study aimed to evaluate the effectiveness of additional molecular genetic testing of cervical canal biopsy samples in detecting endometrial cancer in women with morbid obesity.</p> <p><bold>METHODS:</bold><bold> </bold>Overall, 378 patients with endometrial cancer were examined. Two groups were formed based on comorbid status: the study group (<italic>n</italic> = 103) with morbid obesity and comparison group (<italic>n</italic> = 275) without obesity. The control group included 226 women without oncologic conditions: 47 with morbid obesity and 179 without obesity. Cervical canal samples were collected by brush biopsy. Extracted DNA was amplified using polymerase chain reaction to detect oncogenic mutations in 18 genes.</p> <p><bold>RESULTS:</bold> Oncogenic mutations were identified in endocervical scrapings more frequently in the study group (82.5%; <italic>p</italic> = 0.042) than in the comparison group (72.4%). In the control group, oncogenic mutations were rare and not significantly associated with obesity (8.5% vs 3.9%; <italic>p</italic> = 0.193). In patients with endometrial cancer and morbid obesity, mutation detection increased, and the spectrum of mutated genes was broader. The most informative genes for screening were <italic>PTEN, TP53, PIK3CA, PIK3R1, CTNNB1, KRAS, FBXW7, FGFR2, APC,</italic><italic> </italic>and <italic>POLE.</italic></p> <p><bold>CONCLUSION:</bold> Molecular testing for oncogenic mutations in cervical liquid-based cytology samples is an effective endometrial cancer screening method. The presence of morbid obesity enhances the test’s diagnostic yield and expands the range of detectable mutations.</p></abstract><trans-abstract xml:lang="ru"><p><bold>Актуальность.</bold> Разработка эффективного скрининга для женщин с морбидным ожирением, основанного на доступном и простом получении биологического материала, является крайне актуальной задачей.</p> <p><bold>Цель.</bold> Оценить эффективность дополнительного молекулярно-генетического тестирования соскобов канала шейки матки для выявления рака тела матки на фоне морбидного ожирения.</p> <p><bold>Материал и методы.</bold> Обследованы 378 больных с верифицированным диагнозом рака тела матки. В зависимости от наличия коморбидной патологии сформированы две группы: исследовательская (n=103) с морбидным ожирением и группа сравнения (n=275) без ожирения. Контрольную группу составили 226 женщин без онкологической патологии: 47 больных с морбидным ожирением и 179 без ожирения. Биологический материал из цервикального канала получали методом браш-биопсии. Очищенную ДНК из проб амплифицировали с помощью полимеразной цепной реакции для выявления онкогенных мутаций в 18 генах.</p> <p><bold>Результаты.</bold> В исследовательской группе онкогенные мутации в эндоцервикальных соскобах выявлены в 82,5% случаев, что достоверно чаще (<italic>р</italic>=0,042), чем в группе сравнения (72,4%). В контрольной группе онкогенные мутации были единичными и не различались (<italic>р</italic>=0,193) в зависимости от морбидного ожирения (8,5 против 3,9%). При сочетании рака тела матки и морбидного ожирения частота выявления мутаций генов, связанных с канцерогенезом, возрастала, а спектр мутированных генов был шире. Наиболее информативными для скрининга оказались мутации в генах: <italic>PTEN</italic><italic>, </italic><italic>TP</italic><italic>53, </italic><italic>PIK</italic><italic>3</italic><italic>CA</italic><italic>, </italic><italic>PIK</italic><italic>3</italic><italic>R</italic><italic>1, </italic><italic>CTNNB</italic><italic>1, </italic><italic>KRAS</italic><italic>, </italic><italic>FBXW</italic><italic>7, </italic><italic>FGFR</italic><italic>2, </italic><italic>APC</italic><italic>, </italic><italic>POLE</italic><italic>.</italic></p> <p><bold>Заключение.</bold> Генетическое исследование на онкогенные мутации при выполнении жидкостной цитологии цервикальных соскобов эффективно для скрининга рака тела матки. Наличие морбидного ожирения повышает информативность теста и расширяет спектр выявляемых мутаций.</p></trans-abstract><trans-abstract xml:lang="zh"><p><bold>研究背景：</bold>发展以负担得起和简单生产生物材料为基础的病态肥胖妇女的有效筛查是一项极为紧迫的任务。</p> <p><bold>目的：</bold>以病态肥胖为背景评估宫颈管刮片的额外分子基因检测以检测子宫体癌的有效性。</p> <p><bold>研究对象与方法：</bold>检查了378名确诊为子宫癌的患者。根据合并症病理的存在，形成两组：具有病态肥胖的研究组（<italic>n</italic>=103）和没有肥胖的比较组（<italic>n</italic>=275）。对照组由226名没有癌症的女性组成：47名患有病态肥胖的患者和179名没有肥胖的患者。通过刷活检获得来自宫颈管的生物材料。使用聚合酶链式反应扩增来自样品的纯化DNA，以检测18个基因的致癌突变。</p> <p><bold>结果：</bold>在研究组中82.5％的病例中检测到宫颈刮片的致癌突变，这比比较组（72.4％）显着更常见（<italic>p</italic>=0.042）。在对照组中分离出致癌突变，并且根据病态肥胖（8.5对3.9％）没有差异（<italic>p</italic>=0.193）。随着子宫癌和病态肥胖的组合，与癌变相关的基因突变的检测频率增加，突变基因的范围更广。发现以下基因的突变对于筛选是最有用的：<italic>PTEN</italic>、<italic>TP53</italic>、<italic>PIK3CA</italic>、<italic>PIK3R1</italic>、<italic>CTNNB1</italic>、<italic>KRAS</italic>、<italic>FBXW7</italic>、<italic>FGFR2</italic>、<italic>APC</italic>、<italic>POLE</italic>。</p> <p><bold>结论：</bold>宫颈刮片液细胞学中致癌突变的基因检测对子宫体癌的筛查是有效的。病态肥胖的存在增加了测试的信息价值并扩大了检测到的突变的范围。</p></trans-abstract><kwd-group xml:lang="en"><kwd>endometrial cancer</kwd><kwd>morbid obesity</kwd><kwd>liquid-based cytology</kwd><kwd>molecular genetic testing</kwd><kwd>gene mutations</kwd><kwd>screening</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>рак тела матки</kwd><kwd>морбидное ожирение</kwd><kwd>жидкостная цитология</kwd><kwd>молекулярно-генетическое исследование</kwd><kwd>мутации генов</kwd><kwd>скрининг</kwd></kwd-group><kwd-group xml:lang="zh"><kwd>子宫体癌</kwd><kwd>病态肥胖</kwd><kwd>液体细胞学</kwd><kwd>分子遗传研究</kwd><kwd>基因突变</kwd><kwd>筛查</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Cafforio P, Palmirotta R, Lovero D, et al. Liquid Biopsy in Cervical Cancer: Hopes and Pitfalls. Cancers. 2021;13:3968. doi: 10.3390/cancers13163968 EDN: FMLGBJ</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Kayukova EV. Role of liquid biopsy in the detection and monitoring of cervical cancer. Sibirskij onkologicheskij zhurnal. 2019;18(2):92–101. doi: 10.21294/1814-4861-2019-18-2-92-101 EDN: FWMFMB</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Liang LA, Einzmann T, Franzen A, et al. Cervical Cancer Screening: Comparison of Conventional Pap Smear Test, Liquid-Based Cytology, and Human Papillomavirus Testing as Stand-alone or Cotesting Strategies. Cancer Epidemiol. Biomarkers Prev. 2021;30:474–484. doi: 10.1158/1055-9965 EDN: SNJYIX</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Ma L, Guo H, Zhao Y, et al. Liquid biopsy in cancer current: status, challenges and future prospects. Signal Transduct Target Ther. 2024;9(1):336. doi: 10.1038/s41392-024-02021-w EDN: EHBPZR</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Erickson BK, Kinde I, Dobbin ZC, et al. Detection of somatic TP53 mutations in tampons of patients with high-grade serous ovarian cancer. Obstet Gynecol. 2014;124(5):881–885. doi: 10.1097/AOG.0000000000000484</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Kinde I, Bettegowda C, Wang Y, et al. Evaluation of DNA from the Papanicolaou test to detect ovarian and endometrial cancers. Sci Transl Med. 2013;5(167):167ra4. doi: 10.1126/scitranslmed.3004952</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Wang Y, Li L, Douville C, et al. Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers. Sci Transl Med. 2018;10(433):eaap8793. doi: 10.1126/scitranslmed.aap8793 EDN: VHHWYI</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Hazelwood E, Sanderson E, Tan VY, et al. Identifying molecular mediators of the relationship between body mass index and endometrial cancer risk: a Mendelian randomization analysis. BMC Med. 2022;20(1):125. doi: 10.1186/s12916-022-02322-3 EDN: WPOLTE</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Fang L, Li X, Fang Y, et al. Association between weight-adjusted-waist index and gynecologic cancers: a population-based study. Front Nutr. 2024;11:1449643. doi: 10.3389/fnut.2024.1449643 EDN: QRWKBK</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Kovalenko NV, Kit OI, Maksimov AYu, Demidova AA. Рossibilities of screening for cancer of the uterine body by the content of molecular markers in urine and vaginal-cervical secretion. Klinicheskaya Laboratornaya Diagnostika. 2023;6(3):141–145. doi: 10.51620/0869-2084-2023-68-3-141-145 EDN: LBVIDC</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Kovalenko NV, Kit OI, Maksimov AYu, Demidova AA. Features of the uterine cavity aspirate proteome in patients with endometrial adenocarcinoma and serous cancer of the uterine body. Klinicheskaya Laboratornaya Diagnostika. 2023;68(6):317–322. doi: 10.51620/0869-2084-2023-68-6-317-322 EDN: MUGKUJ</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Jacobs I, Gentry-Maharaj A, Burnell M, et al. Sensitivity of transvaginal ultrasound screening for endometrial cancer in postmenopausal women: a case-control study within the UKCTOCS cohort. Lancet Oncol. 2011;12(1):38–48. doi: 10.1016/S1470-2045(10)70268-0</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Nwabo Kamdje AH, Seke Etet PF, Kipanyula MJ, et al. Insulin-like growth factor-1 signaling in the tumor microenvironment: Carcinogenesis, cancer drug resistance, and therapeutic potential. Front Endocrinol. 2022;13:927390. doi: 10.3389/fendo.2022.927390 EDN: NAYZTU</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Lv J, Liu C, Chen FK, et al. M2 like tumour associated macrophage secreted IGF promotes thyroid cancer stemness and metastasis by activating the PI3K/AKT/mTOR pathway. Mol Med Rep. 2021;24(2):604. doi: 10.3892/mmr.2021.12249</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Wang X, Ding S. The biological and pharmacological connections between diabetes and various types of cancer. Pathol Res Pract. 2021;227:153641. doi: 10.1016/j.prp.2021.153641 EDN: ELTZOT</mixed-citation></ref></ref-list></back></article>
