Molecular alterations in oral carcinogenesis: significant risk predictors in malignant transformation and tumor progression

• Published in: The International journal of biological markers Vol. 22; no. 2; pp. 132 - 143
• Main Authors: SHAH, N. G, TRIVEDI, T. I, VERMA, R. J, TANKSHALI, R. A, GOSWAMI, J. A, SHAH, J. S, JETLY, D. H, KOBAWALA, T. P, PATEL, K. C, SHUKLA, S. N, SHAH, P. M
• Format: Journal Article
• Language: English
• Published: Milano Wichtig 01-04-2007
• Subjects: Adolescent; Adult; Aged; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Biomarkers, Tumor - analysis; Carcinoma, Squamous Cell - pathology; Cell Transformation, Neoplastic; Disease Progression; Female; Fundamental and applied biological sciences. Psychology; Humans; Immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Middle Aged; Mouth Mucosa - cytology; Mouth Mucosa - pathology; Mouth Neoplasms - pathology; Predictive Value of Tests; Reference Values; Tongue - pathology; Tongue Neoplasms - pathology; Oral cancer; Hyperplasia; Biochemistry; Carcinogenesis; Epidemiology; Oncoproteins; Malignant transformation; Clinical biology; Tumor progression; Advanced stage; Risk predictors; Dysplasia; Stomatology; Hyperplasia-dysplasia-early-advanced-carcinoma sequence; Sequence; Malignant tumor; Oral squamous cell carcinoma; C-Onc gene; Risk factor; Oncoprotein; Early; Oral cavity disease; Molecular biology; Predictive factor; Onc gene
• ISSN: 0393-6155; 1724-6008
• DOI: 10.1177/172460080702200207

In this study an attempt was made to establish the significance of a battery of molecular alterations and thereby identify risk predictors in oral carcinogenesis. For this purpose, EGFR, Stat3, H-ras, c-myc, p53, cyclin D1, p16, Rb, Ki-67 and Bcl-2 were localized immunohistochemically in normal mucosa (n=12), hyperplasia (n=35), dysplasia (n=25), early stage carcinoma (n=65) and advanced stage carcinoma (n=70). Deregulation occurred at an early stage and the number of alterations increased with disease progression. Using multivariate logistic regression analysis, the significant risk predictor for hyperplasia from normal mucosa was Ki-67 (OR=5.75, p=0.021); the significant risk predictors for dysplasia from hyperplasia were EGFR (OR=12.96, p=0.002), Stat3 (OR=17.16, p=0.0001), p16 (OR=5.50, p=0.039) and c-myc (OR=5.99, p=0.052); the significant risk predictors for early stage carcinoma from dysplasia were p53 (OR=6.63, p=0.0001) and Rb (OR=3.81, p=0.056); and the significant risk predictors for further progression were EGFR (OR=5.50, p=0.0001), Stat3 (OR=4.49, p=0.0001), H-ras (OR=4.05, p=0.001) and c-myc (OR=2.99, p=0.015). Cyclin D1 holds a key position linking upstream signaling pathways to cell cycle regulation. Gene products of the mitogenic signaling pathway play an equally significant role as cell cycle regulatory proteins in the hyperplasia-dysplasia-early-advanced-carcinoma sequence and together may provide a reference panel of markers for use in defining premalignant lesions and predicting the risk of malignant transformation and tumor progression.