Sheyn I, Noffsinger A E, Heffelfinger S, Davis B, Miller M A, Fenoglio-Preiser C M
Department of Pathology, University of Cincinnati, OH 45267-0529, USA.
Hum Pathol. 1997 Mar;28(3):270-6. doi: 10.1016/s0046-8177(97)90123-4.
Cyclin D1 is a cell-cycle regulator and candidate proto-oncogene implicated in the pathogenesis of numerous tumor types. Amplification of the cyclin D1 gene occurs commonly in esophageal squamous cell carcinomas. However, no studies have examined the role of cyclin D1 in anal carcinogenesis. We examined 20 esophageal squamous cell carcinomas and 24 anal carcinomas for cyclin D1 alterations. Protein expression was evaluated by immunohistochemistry using the cyclin DIGM antibody (Novocastra, Newcastle upon Tyne, UK). Cyclin D1 amplification was examined by fluorescent in situ hybridization (FISH), using a cyclin D1 probe obtained from Toshiya Inaba at St. Jude Children's Research Hospital, Memphis, TN. The FISH sections were analyzed using a Leica (Deerfield, IL) confocal microscope. By immunohistochemistry, 75% of esophageal carcinomas showed evidence of cyclin D1 expression. Cyclin D1 amplification was detected by FISH in 65% of esophageal cancers. There was good correlation between cyclin D1 protein expression and gene amplification, although some tumors showed protein overexpression in the absence of gene amplification. Among the 24 anal carcinomas studied, 8% showed weak cyclin D1 immunoreactivity in rare tumor cells. None of the anal tumors showed cyclin D1 amplification. We conclude that cyclin D1 alterations are common in esophageal carcinomas but do not appear to be important in anal carcinogenesis. Immunohistochemical detection of cyclin D1 protein overexpression is a good predictor of cyclin D1 amplification.
细胞周期蛋白D1是一种细胞周期调节因子，也是一种候选原癌基因，与多种肿瘤类型的发病机制有关。细胞周期蛋白D1基因扩增在食管鳞状细胞癌中很常见。然而，尚无研究探讨细胞周期蛋白D1在肛管癌发生中的作用。我们检测了20例食管鳞状细胞癌和24例肛管癌中细胞周期蛋白D1的改变情况。使用细胞周期蛋白D1GM抗体（诺华卡斯达，英国泰恩河畔纽卡斯尔）通过免疫组织化学评估蛋白表达。使用从田纳西州孟菲斯市圣裘德儿童研究医院的稻叶俊哉处获得的细胞周期蛋白D1探针，通过荧光原位杂交（FISH）检测细胞周期蛋白D1扩增情况。使用徕卡（伊利诺伊州迪尔菲尔德）共聚焦显微镜分析FISH切片。通过免疫组织化学，75%的食管癌显示有细胞周期蛋白D1表达的证据。通过FISH在65%的食管癌中检测到细胞周期蛋白D1扩增。细胞周期蛋白D1蛋白表达与基因扩增之间存在良好的相关性，尽管一些肿瘤在没有基因扩增的情况下显示蛋白过表达。在研究的24例肛管癌中，8%在罕见肿瘤细胞中显示出微弱的细胞周期蛋白D1免疫反应性。没有肛管肿瘤显示细胞周期蛋白D1扩增。我们得出结论，细胞周期蛋白D1改变在食管癌中很常见，但在肛管癌发生中似乎并不重要。细胞周期蛋白D1蛋白过表达的免疫组织化学检测是细胞周期蛋白D1扩增的良好预测指标。
