Yoon Angela J, Shen Jing, Santella Regina M, Zegarelli David J, Chen Rongzhen, Weinstein I B
College of Dental Medicine, Division of Oral and Maxillofacial Pathology, Columbia University Medical Center, 630 West 168th Street, PH15W-1562, New York, NY 10032, USA.
Cancer Epidemiol Biomarkers Prev. 2007 Dec;16(12):2768-72. doi: 10.1158/1055-9965.EPI-07-0659.
Phosphoactivation of a DNA damage response molecule checkpoint kinase 2 (pChk2) may be a marker of oral epithelial cells that have entered the precancerous and squamous cell carcinoma (SCC) stages. We explored whether there was selective expression of pChk2 in precancerous lesions but not in nonneoplastic tissue of the oral mucosa.
In a retrospective cohort design, 96 biopsied clinical leukoplakias and erythroplakias with known subsequent progression to SCC were identified from 48 subjects and assigned as the cases group. Expression status of pChk2 was compared with that of the 97 leukoplakias and erythroplakias that did not progress to SCC (control groups) by immunohistochemical analysis. Included in both groups were lesions with histologically confirmed dysplasia and those that lacked histologic evidence of atypia.
Subjects with pChk2-positive but histology-negative (for atypia) lesions had an 8.6 times higher risk of developing SCC compared with those with pChk2-negative and histology-negative lesions. Overall, the presence of detectable pChk2 staining was able to identify lesions at risk of developing SCC within 3 years with a sensitivity of 85.2%, specificity of 74.2%, and predictive accuracy of 78.2% (odds ratio, 19.9; 95% confidence interval, 7.3-55.5).
This is the first study to include histologically nonatypical cases in the analysis of a putative biomarker for oral precancerous lesions. Our data show that pChk2 merits further investigation as a promising biomarker that can discriminate those lesions at risk for developing SCC, regardless of histologic evidence for atypia.
DNA损伤反应分子检查点激酶2（pChk2）的磷酸化激活可能是已进入癌前和鳞状细胞癌（SCC）阶段的口腔上皮细胞的一个标志物。我们探究了在口腔黏膜的癌前病变中是否存在pChk2的选择性表达，而在非肿瘤性组织中不存在。
在一项回顾性队列设计中，从48名受试者中识别出96例活检的临床白斑和红斑，已知其随后进展为SCC，并将其指定为病例组。通过免疫组织化学分析，将pChk2的表达状态与97例未进展为SCC的白斑和红斑（对照组）进行比较。两组均包括组织学证实有发育异常的病变和缺乏非典型性组织学证据的病变。
与pChk2阴性且组织学阴性的病变相比，pChk2阳性但组织学阴性（非典型性）病变的受试者发生SCC的风险高8.6倍。总体而言，可检测到的pChk2染色能够识别出3年内有发生SCC风险的病变，敏感性为85.2%，特异性为74.2%，预测准确性为
