Panchannavar GS, Angadi PV. Immunohistochemical expression of epithelial mesenchymal transition proteins ZEB1 and E-cadherin in oral leukoplakia and oral squamous cell carcinoma. World J Exp Med 2025; 15(4): 110372 [DOI: 10.5493/wjem.v15.i4.110372]
Corresponding Author of This Article
Punnya V Angadi, MDS, DNB, PhD Deputy Director, Full Professor, Department of Oral and Maxillofacial Pathology, KLE VK Institute of Dental Sciences, KLE Academy of Higher Education and Research, JNMC Campus, Nehrunagar, Belagavi 580010, Karnataka, India. punnya_angadi@rediffmail.com
Research Domain of This Article
Dentistry, Oral Surgery & Medicine
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Exp Med. Dec 20, 2025; 15(4): 110372 Published online Dec 20, 2025. doi: 10.5493/wjem.v15.i4.110372
Immunohistochemical expression of epithelial mesenchymal transition proteins ZEB1 and E-cadherin in oral leukoplakia and oral squamous cell carcinoma
Gouri S Panchannavar, Punnya V Angadi
Gouri S Panchannavar, Department of Oral and Maxillofacial Pathology, DAPM R V Dental College, Bengaluru, Bengaluru 560078, Karnataka, India
Punnya V Angadi, Department of Oral and Maxillofacial Pathology, KLE VK Institute of Dental Sciences, KLE Academy of Higher Education and Research, Belagavi 580010, Karnataka, India
Author contributions: Panchannavar GS carried out the work of method validation, investigation, resource collection and draft; Angadi PV was responsible for the conception, research, validation, writing and review, supervision and project management of the project; Panchannavar GS and Angadi PV carried out the analysis; and all authors thoroughly reviewed and endorsed the final manuscript.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Karanataka Lingayat Education, Vishwanath Katti, Institute of Dental Sceinecs, approval No. 1321.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at punnyarao@kledental-bgm.edu.in. The data is all anonymized.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Punnya V Angadi, MDS, DNB, PhD Deputy Director, Full Professor, Department of Oral and Maxillofacial Pathology, KLE VK Institute of Dental Sciences, KLE Academy of Higher Education and Research, JNMC Campus, Nehrunagar, Belagavi 580010, Karnataka, India. punnya_angadi@rediffmail.com
Received: June 6, 2025 Revised: June 21, 2025 Accepted: September 5, 2025 Published online: December 20, 2025 Processing time: 197 Days and 14.1 Hours
Abstract
BACKGROUND
Oral squamous cell carcinoma (OSCC) is a frequent cancer affecting the oral cavity. OSCC is usually preceded by occurrence of precursor lesions, which demonstrate a varying degree of malignant transformation potential. Epithelial-mesenchymal transition is a significant biological phenomenon that facilitates tumor growth and metastasis through the involvement of diverse epithelial and mesenchymal proteins. E-cadherin down regulation and over-expression of zinc-finger E-box-binding homeobox 1 (ZEB1) has been reported in several cancers.
AIM
To evaluate the role of E-cadherin and ZEB1 in oral leukoplakia and OSCC.
METHODS
A total of 60 cases i.e., oral leukoplakia/oral epithelial dysplasia (OED) (n = 30) and OSCC (n = 30) were included. Immunohistochemistry was performed utilizing two markers: E-cadherin and ZEB1. The Mann-Whitney U test was employed to compare individual markers across the study groups. Spearman’s correlation was done followed by discriminant function analysis.
RESULTS
Reduction in the expression E-cadherin and altered localization were noted from OED to OSCC. Overexpression of ZEB1 along with cytoplasmic accumulation was noted in OED, with marked expression in OSCC. ZEB1 epithelium intensity and ZEB1 connective tissue percentage contributed to the discriminant function with an accuracy of 85% for the classification of OED from OSCC.
CONCLUSION
Loss of E-cadherin and up-regulation of ZEB1 from OED to OSCC, predisposes to induction of epithelial-mesenchymal transition. Discriminant formulas are developed to classify cases of OED and OSCC with 85% accuracy.
Core Tip: The study demonstrates the presence of the epithelial-mesenchymal transition (EMT) phenomenon in oral premalignant and malignant lesions suggesting it to be an early change in carcinogenesis. The loss of E-cadherin and up-regulation of zinc-finger E-box-binding homeobox 1 from oral epithelial dysplasia to oral squamous cell carcinoma corresponds to its role in the induction of EMT and correlated to regional lymph node metastasis, thus promoting tumor progression, invasion, and metastasis. Discriminant formulas have been established to ascertain the malignant potential and to categorize instances of oral epithelial dysplasia and oral squamous cell carcinoma based on the expression of EMT markers which is not previously reported.
