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In the last decade, the incidence rate of detection rate of superficial head, neck and esophageal squamous cell carcinomas has increased with the development of endoscopic imaging techniques. These cancers are thought to arise independently subsequent to tissue exposure to a common carcinogen e.g. alcohol or tobacco. This phenomenon has been termed field cancerization. To determine the molecular background of the development of hypopharyngeal squamous cell carcinomas (HPSCCs) and double esophageal squamous cell carcinomas (DESCCs), the present study immunohistochemically assessed tumor-related protein expression [p53, Fhit (fragile histidine triad), E-cadherin and activation-induced cytidine deaminase (AID)], and subsequently determined the correlation between protein expression and clinicopathological data. Tumor specimens of 9 HPSCCs and 9 DESCCs were endoscopically obtained from 8 patients with HPSCC. The 9 DESCCs, including 5 synchronous and 4 metachronous lesions, were all obtained from four patients with HPSCC. The overexpression of p53 and loss of Fhit expression was immunohistochemically detected in 8 (88.9%) and 8 (88.9%) of the 9 HPSCCs and in 8 (88.9%) and 8 (88.9%) of the 9 DESCCs, respectively, which demonstrated the high frequency of such expression. Additionally, 7 out of 9 HPSCCs, and 7 out of 9 DESCCs demonstrated aberrant expression of p53 and Fhit. The rate of aberrant AID and E-cadherin expression was 67 and 44% in HPSCCs and 44 and 44% in DESCC, respectively. These results suggested that aberrant p53 and Fhit expression was involved in the development of HPSCC and their DESCC, and that their expression may be used for the prediction of DESCC development in patients with HPSCC, thereby acting as a biomarker of field cancerization.

Frequent aberrant p53 and Fhit expression in endoscopically resected superficial hypopharyngeal cancer and esophageal cancer