Sharma Rinu, Sud Neetu, Chattopadhyay Tushar Kant, Ralhan Ranju
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
Oncology. 2005;69(1):10-8. doi: 10.1159/000087283. Epub 2005 Jul 28.
Early detection of esophageal cancer is hampered by paucity of molecular markers for diagnosis of this aggressive gastrointestinal malignancy in early stages. We recently identified TC21/R-Ras2, a small GTP-binding protein (SMG) in esophageal squamous cell carcinomas (ESCCs) by differential display. This study was designed to test the hypothesis that differential expression of TC21 in normal, dysplastic and malignant esophageal tissues may be of clinical relevance in esophageal tumorigenesis.
Immunohistochemical analysis of TC21 was carried out in 83 ESCCs, 37 dysplasias and 29 matched histologically normal esophageal tissues and correlated with clinicopathological parameters. The cellular localization of TC21 was determined by confocal microscopy.
Expression of TC21 protein was observed in 60/83 (73%) ESCCs predominantly localized in tumor nuclei. Intriguingly, intense TC21 immunoreactivity was observed in all endoscopic biopsies with histological evidence of dysplasia (16 cases) as well as in dysplastic areas distant to ESCCs (21 cases), while matched distant histologically normal epithelia did not show detectable TC21 expression. Immunoblotting and semi-quantitative RT-PCR confirmed TC21 expression in dysplastias and ESCCs. Confocal microscopy showed nuclear as well as cytoplasmic TC21 expression in ESCCs and TE13 cells.
To our knowledge, this is the first report demonstrating differential expression of TC21 in normal, dysplastic and ESCC tissues, suggesting that TC21 expression is associated with early stages of esophageal tumorigenesis. Nuclear localization of TC21 makes it the third of over 100 small SMGs identified to be localized in the nucleus.
食管癌的早期检测因缺乏用于诊断这种侵袭性胃肠道恶性肿瘤早期阶段的分子标志物而受到阻碍。我们最近通过差异显示在食管鳞状细胞癌（ESCC）中鉴定出TC21/R-Ras2，一种小GTP结合蛋白（SMG）。本研究旨在检验以下假设：TC21在正常、发育异常和恶性食管组织中的差异表达可能与食管肿瘤发生的临床相关性有关。
对83例ESCC、37例发育异常和29例组织学上匹配的正常食管组织进行TC21的免疫组织化学分析，并与临床病理参数相关联。通过共聚焦显微镜确定TC21的细胞定位。
在60/83（73%）的ESCC中观察到TC21蛋白表达，主要定位于肿瘤细胞核。有趣的是，在所有具有发育异常组织学证据的内镜活检标本（16例）以及远离ESCC的发育异常区域（21例）中均观察到强烈的TC21免疫反应性，而匹配的远处组织学正常上皮未显示可检测到的TC21表达。免疫印迹和半定量RT-PCR证实发育异常和ESCC中存在TC21表达。共聚焦显微镜显示ESCC和TE13细胞中TC21在细胞核以及细胞质中均有表达。
据我们所知，这是第一份证明TC21在正常、发育异常和ESCC组织中差异表达的报告，表明TC21表达与食管肿瘤发生的早期阶段相关。TC21的核定位使其成为已鉴定的100多种定位于细胞核的小SMG中的第三种。
