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.