Yamamoto Sohei, Yashima Kazuo, Kawata Soichiro, Hosoda Kohei, Tamoto Akihiro, Ikebuchi Yuichiro, Matsumoto Kazuya, Kawaguchi Koichiro, Harada Kenichi, Murawaki Yoshikazu, Isomoto Hajime
Division of Medicine and Clinical Science, Faculty of Medicine, University of Tottori, Yonago 683-8504, Japan.
Oncol Lett. 2017 Jul;14(1):587-592. doi: 10.3892/ol.2017.6271. Epub 2017 May 29.
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.
在过去十年中，随着内镜成像技术的发展，头颈部及食管浅表鳞状细胞癌的检出率有所上升。这些癌症被认为是在组织暴露于常见致癌物（如酒精或烟草）后独立发生的。这种现象被称为场癌化。为了确定下咽鳞状细胞癌（HPSCC）和双原发食管鳞状细胞癌（DESCC）发生发展的分子背景，本研究采用免疫组织化学方法评估肿瘤相关蛋白的表达情况（p53、脆性组氨酸三联体蛋白Fhit、E-钙黏蛋白和激活诱导的胞苷脱氨酶AID），随后确定蛋白表达与临床病理数据之间的相关性。从8例HPSCC患者中通过内镜获取了9例HPSCC和9例DESCC的肿瘤标本。9例DESCC，包括5例同步病变和4例异时性病变，均取自4例HPSCC患者。免疫组织化学检测发现，9例HPSCC中有8例（88.9%）p53过表达，8例（88.9%）Fhit表达缺失；9例DESCC中分别有8例（88.9%）和8例（88.9%）出现上述情况，表明这种表达频率较高。此外，9例HPSCC中有7例、9例DESCC中有7例p53和Fhit表达异常。HPSCC中AID和E-钙黏蛋白异常表达率分别为67%和44%，DESCC中分别为44%和44%。这些结果提示，p53和Fhit表达异常参与了HPSCC及其DESCC的发生发展，其表达可能用于预测HPSCC患者DESCC的发生，从而作为场癌化的生物标志物。
