{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T04:33:24Z","timestamp":1793853204436,"version":"4.6.1"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,29]],"date-time":"2023-04-29T00:00:00Z","timestamp":1682726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre","doi-asserted-by":"publisher","award":["2018\/29\/N\/NZ5\/01911"],"award-info":[{"award-number":["2018\/29\/N\/NZ5\/01911"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In the epithelial\u2013mesenchymal transition (EMT) process, cells lose their epithelial phenotype and gain mesenchymal features. This phenomenon was observed in the metastatic phase of neoplastic diseases, e.g., cervical cancer. There are specific markers that are expressed in the EMT. The aim of this study was to determine the localization of and associations between the immunohistochemical (IHC) expression of TWIST, SNAIL, and SLUG proteins in precancerous lesions and cervical cancer. The IHC analysis disclosed higher expressions of EMT markers in precancerous lesions and cervical cancer than in the control group. Moreover, stronger expression of TWIST, SNAIL, and SLUG was observed in cervical intraepithelial neoplasia grade 3 (CIN3) vs. CIN1, CIN3 vs. CIN2, and CIN2 vs. CIN1 cases (p &lt; 0.05). In cervical cancer, IHC reactions demonstrated differences in TWIST, SNAIL, and SLUG expression in grade 1 (G1) vs. grade 2 (G2) (p &lt; 0.0011; p &lt; 0.0017; p &lt; 0.0001, respectively) and in G1 vs. grade 3 (G3) (p &lt; 0.0029; p &lt; 0.0005; p &lt; 0.0001, respectively). The results of our study clearly showed that existing differences in the expression of the tested markers in precancerous vs. cancerous lesions may be utilized in the diagnosis of cervical cancer. Further studies on bigger populations, as well as in comparison with well-known markers, may improve our outcomes.<\/jats:p>","DOI":"10.3390\/ijms24098063","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T13:54:46Z","timestamp":1682949286000},"page":"8063","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The Immunohistochemical Expression of Epithelial\u2013Mesenchymal Transition Markers in Precancerous Lesions and Cervical Cancer"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5746-4824","authenticated-orcid":false,"given":"Aneta","family":"Popiel-Kopaczyk","sequence":"first","affiliation":[{"name":"Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4093-7386","authenticated-orcid":false,"given":"Aleksandra","family":"Piotrowska","sequence":"additional","affiliation":[{"name":"Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrycja","family":"Sputa-Grzegrzolka","sequence":"additional","affiliation":[{"name":"Division of Anatomy, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3168-062X","authenticated-orcid":false,"given":"Beata","family":"Smolarz","sequence":"additional","affiliation":[{"name":"Department of Pathology, Polish Mother\u2019s Memorial Hospital Research Institute, 93-338 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Romanowicz","sequence":"additional","affiliation":[{"name":"Department of Pathology, Polish Mother\u2019s Memorial Hospital Research Institute, 93-338 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Dziegiel","sequence":"additional","affiliation":[{"name":"Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland"},{"name":"Department of Physiotherapy, University School of Physical Education, 51-612 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzenna","family":"Podhorska-Okolow","sequence":"additional","affiliation":[{"name":"Division of Ultrastructural Research, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8023-8585","authenticated-orcid":false,"given":"Christopher","family":"Kobierzycki","sequence":"additional","affiliation":[{"name":"Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"815213","DOI":"10.3389\/fonc.2021.815213","article-title":"A Comparative Study on the Accuracy and Efficacy Between Dalton and CINtec\u00ae PLUS p16\/Ki-67 Dual Stain in Triaging HPV-Positive Women","volume":"11","author":"Li","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_2","unstructured":"(2022, May 22). Cervical Cancer\u2014Cancer Stat Facts, Available online: https:\/\/seer.cancer.gov\/statfacts\/html\/cervix.html."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e12770","DOI":"10.1007\/s12253-018-0488-3","article-title":"The Role of Testin in Human Cancers","volume":"25","author":"Popiel","year":"2019","journal-title":"Pathol. Oncol. Res."},{"key":"ref_4","unstructured":"(2022, June 13). Cervical Cancer: Statistics|Cancer.Net. Available online: https:\/\/www.cancer.net\/cancer-types\/cervical-cancer\/statistics."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S0140-6736(97)02250-2","article-title":"Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer","volume":"350","author":"Landoni","year":"1997","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.ijrobp.2005.10.019","article-title":"A phase III randomized trial of postoperative pelvic irradiation in stage IB cervical carcinoma with poor prognostic features: Follow-up of a gynecologic oncology group study","volume":"65","author":"Rotman","year":"2006","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/0090-8258(90)90072-S","article-title":"Prospective surgical-pathological study of disease-free interval in patients with stage IB squamous cell carcinoma of the cervix: A Gynecologic Oncology Group study","volume":"38","author":"Delgado","year":"1990","journal-title":"Gynecol. Oncol."},{"key":"ref_8","unstructured":"(2022, June 13). SEER Cancer Statistics Review 1975\u20132003\u2014Previous Version\u2014SEER Cancer Statistics, Available online: https:\/\/seer.cancer.gov\/archive\/csr\/1975_2003\/."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4743","DOI":"10.1158\/1078-0432.CCR-08-0234","article-title":"Epithelial-Mesenchymal Transition in Cervical Cancer: Correlation with Tumor Progression, Epidermal Growth Factor Receptor Overexpression, and Snail Up-Regulation","volume":"14","author":"Lee","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Li, J., and Zhou, B.P. (2011). Activation of \u03b2-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters. BMC Cancer, 11.","DOI":"10.1186\/1471-2407-11-49"},{"key":"ref_11","first-page":"1","article-title":"Epithelial-mesenchymal transition in cervical carcinoma","volume":"4","author":"Lee","year":"2012","journal-title":"Am. J. Transl. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1093\/annonc\/mdm344","article-title":"Twist expression in patients with cervical cancer is associated with poor disease outcome","volume":"19","author":"Shibata","year":"2008","journal-title":"Ann. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.3892\/or.2012.1633","article-title":"Short hairpin RNA targeting Twist1 suppresses cell proliferation and improves chemosensitivity to cisplatin in HeLa human cervical cancer cells","volume":"27","author":"Zhu","year":"2012","journal-title":"Oncol. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1016\/j.humpath.2014.05.001","article-title":"Twist2, the key Twist isoform related to prognosis, promotes invasion of cervical cancer by inducing epithelial-mesenchymal transition and blocking senescence","volume":"45","author":"Wang","year":"2014","journal-title":"Hum. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.3892\/or.2015.4143","article-title":"Twist induces epithelial-mesenchymal transition in cervical carcinogenesis by regulating the TGF-\u03b2\/Smad3 signaling pathway","volume":"34","author":"Fan","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.humpath.2005.12.021","article-title":"High Twist expression is involved in infiltrative endometrial cancer and affects patient survival","volume":"37","author":"Kyo","year":"2006","journal-title":"Hum. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s10565-010-9163-5","article-title":"Snail regulates cell survival and inhibits cellular senescence in human metastatic prostate cancer cell lines","volume":"26","author":"Baygi","year":"2010","journal-title":"Cell Biol. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/j.cellbi.2007.03.023","article-title":"Zinc-finger transcription factor Snail accelerates survival, migration and expression of matrix metalloproteinase-2 in human bone mesenchymal stem cells","volume":"31","author":"Zha","year":"2007","journal-title":"Cell Biol. Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1101\/gad.294104","article-title":"Snail blocks the cell cycle and confers resistance to cell death","volume":"18","author":"Vega","year":"2004","journal-title":"Genes Dev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.ccr.2009.01.023","article-title":"Cancer Metastasis Is Accelerated through Immunosuppression during Snail-Induced EMT of Cancer Cells","volume":"15","author":"Shirako","year":"2009","journal-title":"Cancer Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"199","DOI":"10.4161\/cam.4.2.10943","article-title":"Snail: More than EMT","volume":"4","author":"Wu","year":"2010","journal-title":"Cell Adhes. Migr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"41650","DOI":"10.18632\/oncotarget.9519","article-title":"Lnc-CC3 increases metastasis in cervical cancer by increasing Slug expression","volume":"7","author":"Jiang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7911","DOI":"10.1002\/jcp.29446","article-title":"Long noncoding RNA SNHG12 modulated by human papillomavirus 16 E6\/E7 promotes cervical cancer progression via ERK\/Slug pathway","volume":"235","author":"Lai","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1186\/s12935-021-01858-3","article-title":"Absence of EpCAM in cervical cancer cells is involved in slug induced epithelial-mesenchymal transition","volume":"21","author":"Liu","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"26152","DOI":"10.18632\/oncotarget.8434","article-title":"Slug inhibits the proliferation and tumor formation of human cervical cancer cells by up-regulating the p21\/p27 proteins and down-regulating the activity of the Wnt\/\u03b2-catenin signaling pathway via the trans-suppression Akt1\/p-Akt1 expression","volume":"7","author":"Cui","year":"2016","journal-title":"Oncotarget"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1038\/s41388-022-02202-3","article-title":"Downregulation of LNMAS orchestrates partial EMT and immune escape from macrophage phagocytosis to promote lymph node metastasis of cervical cancer","volume":"41","author":"Liao","year":"2022","journal-title":"Oncogene"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1159\/000320174","article-title":"Defining the E-Cadherin Repressor Interactome in Epithelial-Mesenchymal Transition: The PMC42 Model as a Case Study","volume":"193","author":"Hugo","year":"2011","journal-title":"Cells Tissues Organs"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3645","DOI":"10.1158\/0008-5472.CAN-07-2938","article-title":"Loss of E-Cadherin Promotes Metastasis via Multiple Downstream Transcriptional Pathways","volume":"68","author":"Onder","year":"2008","journal-title":"Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"166","DOI":"10.18632\/oncotarget.801","article-title":"TIMP-2 modulates cancer cell transcriptional profile and enhances E-cadherin\/beta-catenin complex expression in A549 lung cancer cells","volume":"4","author":"Bourboulia","year":"2013","journal-title":"Oncotarget"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s00535-012-0720-y","article-title":"Serrated polyps of the large intestine: Current understanding of diagnosis, pathogenesis, and clinical management","volume":"48","author":"Rosty","year":"2012","journal-title":"J. Gastroenterol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1002\/cncy.22192","article-title":"Age-specific 3-year cumulative risk of cervical cancer and high-grade dysplasia on biopsy in 9434 women who underwent HPV cytology cotesting","volume":"127","author":"Ge","year":"2019","journal-title":"Cancer Cytopathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1093\/ajcp\/112.1.57","article-title":"Long-term outcome and relative risk in women with atypical squamous cells of undetermined significance","volume":"112","author":"Raab","year":"1999","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"E223","DOI":"10.25011\/cim.v36i4.19956","article-title":"Snail family proteins in cervical squamous carcinoma: Expression and significance","volume":"36","author":"Zhao","year":"2013","journal-title":"Clin. Investig. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.canlet.2014.09.021","article-title":"EMT in cervical cancer: Its role in tumour progression and response to therapy","volume":"356","author":"Qureshi","year":"2015","journal-title":"Cancer Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"420891","DOI":"10.1155\/2015\/420891","article-title":"EMT-Inducing Molecular Factors in Gynecological Cancers","volume":"2015","author":"Campo","year":"2015","journal-title":"Biomed Res Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"22","DOI":"10.3389\/fmolb.2020.00022","article-title":"Combined Snail and E-cadherin Predicts Overall Survival of Cervical Carcinoma Patients: Comparison Among Various Epithelial-Mesenchymal Transition Proteins","volume":"7","author":"Tian","year":"2020","journal-title":"Front. Mol. Biosci."},{"key":"ref_37","first-page":"1451","article-title":"HMQ-T-F2 suppresses migration of the human cervical cancer HeLa cells by reversing EMT via the PI3K\/Akt signaling pathway","volume":"42","author":"Dai","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1158\/1535-7163.MCT-20-0316","article-title":"EMT-Induced Gemcitabine Resistance in Pancreatic Cancer Involves the Functional Loss of Equilibrative Nucleoside Transporter 1","volume":"20","author":"Weadick","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/cns.13297","article-title":"Elevation of CXCL1 indicates poor prognosis and radioresistance by inducing mesenchymal transition in glioblastoma","volume":"26","author":"Alafate","year":"2020","journal-title":"CNS Neurosci. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1080\/21691401.2020.1716779","article-title":"Inhibition of Wnt signalling pathway by XAV939 enhances radiosensitivity in human cervical cancer HeLa cells","volume":"48","author":"Zhang","year":"2020","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_41","first-page":"e923799","article-title":"WNT974 Inhibits Proliferation, Induces Apoptosis, and Enhances Chemosensitivity to Doxorubicin in Lymphoma Cells by Inhibiting Wnt\/\u03b2-Catenin Signaling","volume":"26","author":"Chen","year":"2020","journal-title":"Experiment"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"490","DOI":"10.3390\/cimb45010032","article-title":"The Expression of Testin, Ki-67 and p16 in Cervical Cancer Diagnostics","volume":"45","author":"Grzegrzolka","year":"2023","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.1002\/imt2.5","article-title":"ImageGP: An easy-to-use data visualization web server for scientific researchers","volume":"1","author":"Chen","year":"2022","journal-title":"Imeta"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/8063\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:26:36Z","timestamp":1760124396000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/8063"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,29]]},"references-count":43,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ijms24098063"],"URL":"https:\/\/doi.org\/10.3390\/ijms24098063","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,29]]}}}