Savci-Heijink Cemile Dilara, Kosari Farhad, Aubry Marie-Christine, Caron Bolette L, Sun Zhifu, Yang Ping, Vasmatzis George
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Am J Pathol. 2009 May;174(5):1629-37. doi: 10.2353/ajpath.2009.080778. Epub 2009 Mar 26.
Results from several microarray-based studies have led to the identification of up-regulated expression levels of the DSG3 gene in pulmonary squamous cell carcinomas (SQCCs). The purpose of this study was to determine the role of DSG3 expression in the diagnosis of SQCCs of the lung and to compare DSG3 with p63, CK5, and CK6, as markers of squamous cell differentiation. Expression of DSG3 mRNA was evaluated in bulk laser capture microdissection-derived microarray data and by quantitative reverse transcription PCR on both SQCCs and adenocarcinomas. Expression levels of p63, CK5, and CK6 were evaluated in microarray data from the same set. An immunohistochemical study using antibodies directed against DSG3, p63, and CK5/6 was also performed. DSG3 was over-expressed in SQCCs but had very limited expression in both adenocarcinomas and non-neoplastic lungs. The microarray data showed that DSG3 had a sensitivity and specificity of 88% and 98%, respectively, in detecting SQCC versus adenocarcinoma. In comparison, sensitivity and specificity was 92% and 82% for p63, and 85% and 96% for CK5, respectively. The correlation coefficient between the microarray and immunohistochemical data for these genes was greater than or equal to 0.9. Using immunohistochemistry, sensitivity and specificity of DSG3 for lung cancers were 98% and 99%, respectively. Therefore, DSG3 can be a useful ancillary marker to separate SQCC from other subtypes of lung cancer.
多项基于微阵列的研究结果已导致在肺鳞状细胞癌(SQCC)中鉴定出桥粒芯糖蛋白3(DSG3)基因表达水平上调。本研究的目的是确定DSG3表达在肺SQCC诊断中的作用,并将DSG3与作为鳞状细胞分化标志物的p63、细胞角蛋白5(CK5)和细胞角蛋白6(CK6)进行比较。在批量激光捕获显微切割获得的微阵列数据中以及通过对SQCC和腺癌进行定量逆转录PCR来评估DSG3 mRNA的表达。在来自同一组的微阵列数据中评估p63、CK5和CK6的表达水平。还进行了一项使用针对DSG3、p63和CK5/6的抗体的免疫组织化学研究。DSG3在SQCC中过表达,但在腺癌和非肿瘤性肺组织中的表达非常有限。微阵列数据显示,DSG3在检测SQCC与腺癌时的敏感性和特异性分别为88%和98%。相比之下,p63的敏感性和特异性分别为92%和82%,CK5的敏感性和特异性分别为85%和96%。这些基因的微阵列数据与免疫组织化学数据之间的相关系数大于或等于0.9。使用免疫组织化学,DSG3对肺癌的敏感性和特异性分别为98%和99%。因此,DSG3可以作为一种有用的辅助标志物,用于将SQCC与其他肺癌亚型区分开来。