Department of Oral and Maxillofacial Surgery, University of Regensburg, Regensburg, Germany.
Proteomics Clin Appl. 2007 May;1(5):486-93. doi: 10.1002/prca.200600669. Epub 2007 Apr 4.
In oral mucosa lesions it is frequently difficult to differentiate between precursor lesions and already manifest oral squamous cell carcinoma. Therefore, multiple scalpel biopsies are necessary to detect tumor cells already in early stages and to guarantee an accurate follow-up. We analyzed oral brush biopsies (n = 49) of normal mucosa, inflammatory and hyperproliferative lesions, and oral squamous cell carcinoma with ProteinChip Arrays (SELDI) as a non-invasive method to characterize putative tumor cells. Three proteins were found that differentiated between these three stages. These three proteins are able to distinguish between normal cells and tumor cells with a sensitivity of 100% and specificity of 91% and can distinguish inflammatory/hyperproliferative lesions from tumor cells with a sensitivity of up to 91% and specificity of up to 90%. Two of these proteins have been identified by immunodepletion as S100A8 and S100A9 and this identification was confirmed by immunocytochemistry. For the first time, brush biopsies have been successfully used for proteomic biomarker discovery. The identified protein markers are highly specific for the distinction of the three analyzed stages and therewith reflect the progression from normal to premalignant non-dysplastic and finally to tumor tissue. This knowledge could be used as a first diagnostic step in the monitoring of mucosal lesions.
在口腔黏膜病变中，通常难以区分前驱病变和已经表现出的口腔鳞状细胞癌。因此，需要进行多次手术刀活检，以检测早期的肿瘤细胞，并保证准确的随访。我们使用蛋白质芯片阵列（SELDI）分析了正常黏膜、炎症和增生性病变以及口腔鳞状细胞癌的口腔刷活检（n=49），这是一种非侵入性方法，可以鉴定潜在的肿瘤细胞。发现了三种能够区分这三个阶段的蛋白质。这三种蛋白质能够以 100%的敏感性和 91%的特异性区分正常细胞和肿瘤细胞，并能够以高达 91%的敏感性和高达 90%的特异性区分炎症/增生性病变与肿瘤细胞。其中两种蛋白质通过免疫耗竭被鉴定为 S100A8 和 S100A9，免疫细胞化学也证实了这一鉴定。这是首次成功地将刷活检用于蛋白质组生物标志物的发现。所鉴定的蛋白质标记物对于区分这三个分析阶段具有高度特异性，反映了从正常到癌前非发育不良，最终到肿瘤组织的进展。这些知识可以用作监测黏膜病变的初步诊断步骤。
