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Clinicopathological Features and Prognostic Implications of Loss of K5 and Gain of K1, K8 and K18 in Oral Potentially Malignant Lesions and Squamous Cell Carcinomas: An Immunohistochemical Analysis

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Aims: To analyze alterations in the expression and localization patterns of keratins-K1, K5, K8 and K18 using immunohistochemistry and correlate with clinicopathological parameters of patients with oral potentially malignant lesions and squamous cell carcinomas to evaluate diagnostic and prognostic implications of loss and gain of keratins. Methods: Altered keratin expression pattern was investigated using immunohistochemistry in tissues of oral normal mucosa (n=10), leukoplakia (n=50), submucous fibrosis (n=67) and tumor respective cut-margins (n=304). The prognostic significance was determined by correlating the values of these two events singly as well as in different permutations and combinations with clinicopathological parameters using univariate and multivariate analyzes. Results: Loss of K5 and aberrant expression of K1, K8 and K18 were seen in oral premalignant lesions as well as tumor tissues in comparison to normal oral mucosal tissues. Non-expression of K5 (p=0.003), and aberrant expression of K1 (p<0.001), K8 (p=0.001), and K18 (p=0.004), independently significantly correlated with clinicopathological progressive grade of oral premalignant disorders as well as some of the clinicopathological factors of patients with oral cancer. The univariate and multivariate analysis showed the significance of combination of keratin markers (K1, K8, K18) on overall survival and local recurrence free survival of patients with oral cancer. The number of markers combined together has increased the risk of recurrence significantly (p<0.0001). Conclusion: These findings suggest, loss and gain of keratins could serve as surrogate markers for the diagnosis of oral potentially malignant disorders and may also have prognostic value in patients with oral cancer.

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