Evaluation of TGF-α and EGFR Expression in Oral Leukoplakia and Oral Submucous Fibrosis by Quantitative Immunohistochemistry

Abstract

Objective: Oral leukoplakia (OL) and oral submucous fibrosis (OSMF) are clinically distinct preneoplastic states that precede the development of oral squamous cell carcinoma. Recently, attempts are being made to identify specific molecular event(s) as prognostic markers to identify oral precancerous lesions with higher malignant potential. The goal of the present study was to evaluate the expression of EGFR and its ligand TGF-α in OL with dysplasia and OSMF as intermediate markers of malignancy by quantitative immunohistochemistry. Methods: Oral tissues were stained with monoclonal antibodies to TGF-α and EGFR. The results were analyzed with Photoquant image analysis software. Results: The expression of TGF-α and EGFR was upregulated in OL, OSMF and oral squamous cell carcinomas relative to normal oral mucosa. The area and intensity of staining of TGF-α in the proliferative layers (stratum germinativum) increased linearly in OL with mild, moderate and severe dysplasia as compared to control mucosa (p < 0.05). EGFR levels increased linearly in the stratum spinosum in OL with increasing degrees of dysplasia (p < 0.05). In general, the expression of both proteins in OSMF was similar to that in OL with moderate dysplasia. Conclusions: EGFR and TGF-α represent early markers of malignancy in OL with dysplasia. Quantitative measurement of these proteins may provide intermediate endpoints in prospective chemopreventive trials.

MIEN1 promotes oral cancer progression and implicates poor overall survival

“…3 Extensive research demonstrates the importance of various oncogenes and tumor suppressors along with associated signal transduction pathways in oral cancer progression. [5][6][7][8][9] It is evident that many of these pathways converge to facilitate invasion and migration of cells to the lymph nodes, characteristic of OSCC. Migration and invasion of cancer cells are hallmarks of cancer metastasis, 10,11 facilitated by processes including loss of cell adhesion and epithelial properties, cytoskeletal rearrangement, gain of mesenchymal form and ability to cleave the extracellular matrix by secreting proteases, and formation of new blood vessels by secreting angiogenic factors.…”

Gene Expression Differences in Normal Esophageal Mucosa Associated with Regression and Progression of Mild and Moderate Squamous Dysplasia in a High-Risk Chinese Population

“…TGF-a, for example, is often overexpressed in head and neck and other squamous cell carcinomas and is believed to be a potent mitogen involved in wound healing (42). Its overexpression is thought to be an early event, found in both dysplasia and normal mucosa surrounding dysplastic tissue (43,44). Two other potent mitogens, MET and RET, which are tyrosine kinase proto-oncogenes, are also involved in a variety of cancers (45,46).…”

Marcadores de senescencia celular en cáncer y precáncer oral

“…Por otro lado hay estudios que han presentado como marcadores de progresión el aumento expresión de EGFR y de TGF-α, pero con unos resultados y rangos de porcentaje muy poco precisos para determinar en que situación de malignidad nos encontramos (26).…”