Role of Epithelial-Mesenchymal Transition Markers and Hormonal Receptor Expression in the Immature Polypoid Squamous Metaplasia
Cervical intraepithelial neoplasia (CIN) is a key precursor to cervical cancer, and understanding the molecular mechanisms underlying its progression is critical for improving diagnostic and therapeutic strategies. Immature polypoid squamous metaplasia (IPSM) represents a distinct histological entity that may play a role in the progression of CIN. This study aimed to investigate the expression of epithelial-mesenchymal transition (EMT) markers (vimentin, beta-catenin, and E-cadherin) and hormonal receptors (estrogen receptor [ER] and progesterone receptor [PR]) in various stages of CIN, including IPSM.A total of 195 patients with reactive ectocervix, mature squamous metaplasia, IPSM, and CIN (CIN 1 and CIN 2) were included. Immunohistochemical staining was performed to assess the expression of vimentin, beta-catenin, E-cadherin, ER, and PR. HPV status was also determined, and the correlation between marker expression and histological grade was analysed. The study found significant upregulation of vimentin and beta-catenin expression and a loss of E-cadherin in CIN lesions, particularly in CIN 2. HPV-positive cases exhibited higher expression of EMT markers and more pronounced loss of E-cadherin compared to HPV-negative cases. Additionally, ER and PR expression was significantly reduced in higher-grade CIN lesions. These molecular changes were strongly associated with progressing from lower-grade CIN and IPSM to CIN 2. Our findings suggest that the upregulation of EMT markers and the downregulation of hormonal receptors play key roles in the progression of CIN. These markers, particularly vimentin, beta-catenin, and E-cadherin, may be valuable biomarkers for early detection and risk stratification in cervical cancer prevention. Future research should explore the therapeutic potential of targeting these molecular pathways, particularly in HPV-positive CIN lesions.
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R. Cappellesso et al., “The prognostic role of the epithelial-mesenchymal transition markers E-cadherin and Slug in laryngeal squamous cell carcinoma,” Histopathology, vol. 67, no. 4, pp. 491–500, Oct. 2015, doi: 10.1111/HIS.12668.
A. Auluck, G. Hislop, C. Bajdik, C. Poh, L. Zhang, and M. Rosin, “Trends in oropharyngeal and oral cavity cancer incidence of Human Papillomavirus (HPV)-related and HPV-unrelated sites in a multicultural population: The British Columbia experience,” Cancer, vol. 116, no. 11, pp. 2635–2644, Jun. 2010, doi: 10.1002/CNCR.25087.
N. A. Andrews, A. S. Jones, T. R. Helliwell, and A. R. Kinsella, “Expression of the E-cadherin-catenin cell adhesion complex in primary squamous cell carcinomas of the head and neck and their nodal metastases,” Br J Cancer, vol. 75, no. 10, pp. 1474–1480, 1997, doi: 10.1038/BJC.1997.252.
M. Lefevre et al., “Epithelial to mesenchymal transition and HPV infection in squamous cell oropharyngeal carcinomas: the papillophar study,” Br J Cancer, vol. 116, no. 3, p. 362, Jan. 2017, doi: 10.1038/BJC.2016.434.
S. Pirouzpanah, F. A. Taleban, P. Mehdipour, S. Sabour, and M. Atri, “Hypermethylation pattern of ESR and PgR genes and lacking estrogen and progesterone receptors in human breast cancer tumors: ER/PR subtypes,” Cancer Biomarkers, vol. 21, no. 3, pp. 621–638, 2018, doi: 10.3233/CBM-170697.
W. Truin, R. M. H. Roumen, S. Siesling, K. K. van de Vijver, V. C. G. Tjan-Heijnen, and A. C. Voogd, “Estrogen and progesterone receptor expression levels do not differ between lobular and ductal carcinoma in patients with hormone receptor-positive tumors,” Breast Cancer Res Treat, vol. 164, no. 1, pp. 133–138, Jul. 2017, doi: 10.1007/s10549-017-4220-x.
R. G. Lapidus, S. J. Nass, and N. E. Davidson, “The loss of estrogen and progesterone receptor gene expression in human breast cancer,” J Mammary Gland Biol Neoplasia, vol. 3, no. 1, pp. 85–94, 1998, doi: 10.1023/A:1018778403001.
M. Branca et al., “Upregulation of nuclear factor-κB (NF-κB) is related to the grade of cervical intraepithelial neoplasia, but is not an independent predictor of high-risk human papillomavirus or disease outcome in cervical cancer,” Diagn Cytopathol, vol. 34, no. 8, pp. 555–563, Aug. 2006, doi: 10.1002/dc.20514.
K. J. Syrjänen, “Spontaneous evolution of intraepithelial lesions according to the grade and type of the implicated human papillomavirus (HPV),” European Journal of Obstetrics and Gynecology and Reproductive Biology, vol. 65, no. 1, pp. 45–53, 1996, doi: 10.1016/0028-2243(95)02303-A.
M. J. Arends, C. H. Buckley, and M. Wells, “Aetiology, pathogenesis, and pathology of cervical neoplasia,” J Clin Pathol, vol. 51, no. 2, pp. 96–103, 1998, doi: 10.1136/jcp.51.2.96.
J. A. Glenn et al., “Longitudinal patterns of recurrence in patients with adrenocortical carcinoma,” Surgery (United States), vol. 165, no. 1, pp. 186–195, Jan. 2019, doi: 10.1016/J.SURG.2018.04.068.
M. Branca et al., “Up-regulation of proliferating cell nuclear antigen (PCNA) is closely associated with high-risk human papillomavirus (HPV) and progression of cervical intraepithelial neoplasia (CIN), but does not predict disease outcome in cervical cancer,” European Journal of Obstetrics and Gynecology and Reproductive Biology, vol. 130, no. 2, pp. 223–231, 2007, doi: 10.1016/j.ejogrb.2006.10.007.
M. Shen and Y. Kang, “Role Reversal: A Pro-metastatic Function of E-Cadherin,” Dev Cell, vol. 51, no. 4, pp. 417–419, Nov. 2019, doi: 10.1016/J.DEVCEL.2019.10.028.
T. Svanadze, S. Kepuladze, N. Tevzadze, and G. Burkadze, “ASSESSMENT OF PROLIFERATIVE ACTIVITY OF DIFFERENT TYPES OF SQUAMOUS CELL METAPLASIA OF THE CERVIX USING AgNor TECHNOLOGY,” ქართველი მეცნიერები, vol. 5, no. 2, pp. 275–287, Jun. 2023, doi: 10.52340/gs.2023.05.02.35.
S. Boulenouar et al., “Effects of HPV-16 E5, E6 and E7 proteins on survival, adhesion, migration and invasion of trophoblastic cells,” Carcinogenesis, vol. 31, no. 3, pp. 473–480, Mar. 2010, doi: 10.1093/CARCIN/BGP281.
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