Pathological and molecular analysese of multiple esophageal cancers.

食管鳞状细胞癌多起源于东亚国家，如中国和日本。病毒感染、饮酒和吸烟习惯被认为是食管癌的发病机制，但其具体发生机制尚不清楚。醛酮还原酶（Aldo-keto reductase，AKR）是一种单体可溶性NAD（P）H依赖性氧化还原酶，催化多种羰基化合物的还原。AKR参与消除反应，因为它们通常将醛或酮上的羰基官能化以形成伯醇或仲醇。我们最近发现AKR家族1成员B10（AKR 1B 10）的过度表达与吸烟者的非小细胞肺癌之间存在高度相关性。AKR 1B 10在鳞状细胞癌（SCC）中的高表达率尤为明显。本研究的目的是分析AKR 1B 10在食管和头颈部正常鳞状上皮和鳞状细胞癌及其他病变中的表达。使用抗AKR 1B 10抗体对总共289个标本进行免疫组织化学，包括非肿瘤性和癌前病变、食管SCC（ESCC）和头颈部SCC（HNSCC）。结果显示，AKR 1 B10的过表达仅在SCC中观察到，显示出弥漫性和强免疫反应性，尽管一些非肿瘤性病变和癌前病变的病例显示出显著的过表达。有趣的是，疣状癌中AKR 1B 10的过表达趋势很强，高分化鳞癌中AKR 1B 10的过表达似乎也高于中分化和低分化鳞癌。我们的研究表明，AKR 1 B10是一个潜在的良好的诊断标志物ESCC和HNSCC。结合本研究的结果和以往的研究结果，我们认为AKR 1B 10可能是一个潜在的致癌因子，其过表达的意义与AKR 1家族的生理功能有关。

Squamous cell carcinoma of the esophagus is frequently originated from east Asian countries, such as China and Japan. Virus infection, alcohol drinking and smoking habit were assumed to be pathogenesis of esophageal cancers, however detailed mechanism of carcinogenesis has not been well understood yet. Aldo-keto reductase (AKR) is monomeric soluble NAD (P) H-dependent oxidoreductase that catalyzes the reduction of a variety of carbonyl compounds. AKRs are involved in elimination reactions, because they will often functionalize carbonyl groups on aldehydes or ketones to form primary or secondary alcohols. We recently identified high correlation between the overexpression of the AKR family 1 member B10 (AKR1B10) and smokers' non-small cell lung carcinomas. Especially in squamous cell carcinoma (SCC), overexpression of AKR1B10 was observed in a high incidence. The aim of current study was to analyze the expression of AKR1B10 in normal squamous epithelium and SCC or other lesions in esophagus and head and neck region. Immunohistochemistry was performed on total 289 specimens including non-neoplastic and pre-malignant lesions, esophageal SCC (ESCC) and head and neck SCC (HNSCC), using antibodies against AKR1B10. As the results, overexpression of AKR1 B10 showing the diffuse and strong immunoreactivity was observed only in SCCs, although some cases of non-neoplastic lesions and pre-malignant lesions showed significant overexpression. Interestingly, verrucous carcinoma demonstrated strong tendency to over-express AKR1B10 and well differentiated SCC also seemed to over-express more than moderate and poorly differentiated one. Our study shows that AKR1 B10 is a potently good diagnostic marker for ESCC and HNSCC. Moreover, we suggest the potential carcinogenic factor ofAKR1B10 about the significance of its overexpression, taken together with the results of this study and previous reports demonstrating the physiological function of AKR1 family.