Liu S C, Sauter E R, Clapper M L, Feldman R S, Levin L, Chen S Y, Yen T J, Ross E, Engstrom P F, Klein-Szanto A J
Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Cancer Epidemiol Biomarkers Prev. 1998 Jul;7(7):597-603.
The expression of several markers of epithelial cell proliferation was analyzed to establish baseline data for future chemoprevention studies of oral premalignant lesions. Punch biopsies (n = 60) from three different sites of oral mucosa (bucca, lateral tongue, and the floor of the mouth) were obtained from 20 normal donors of both sexes. After formaldehyde fixation and paraffin embedding, immunohistochemistry was used to detect the proliferation markers Mib-1, cyclin D1, and centromere-associated protein CENP-F. Analysis of sections stained for the three markers showed similar patterns, i.e., a low labeling index (LI) in the basal layer and a high LI in the parabasal layer at all three intraoral sites. No proliferative activity was seen above the parabasal layer (superficial layer). All sites showed similar Mib-1 LI values for the proliferative markers. The tongue epithelium exhibited higher parabasal LIs of cyclin D1 and CENP-F than did the other two sites. No significant differences were detected between smokers and nonsmokers. The data from normal mucosa were compared with those from low (n = 30)- and high (n = 17)-grade dysplastic leukoplakias. The Mib-1 LI showed a very significant change, with a 9-fold increase in the basal layer LI in dysplastic leukoplakias. Cyclin D1 and CENP-F showed similar trends with increments of up to 7-fold in the basal layer of high-grade dysplasia. Although the proliferative activity of the parabasal layer was similar in normal and leukoplakic epithelia, the superficial layer showed a significant increment in proliferative activity mainly in high-grade leukoplakia. These studies suggest that proliferation markers in the basal and superficial cells of premalignant lesions may serve as surrogate end point biomarkers for chemoprevention trials.
分析了几种上皮细胞增殖标志物的表达情况，以建立口腔癌前病变未来化学预防研究的基线数据。从20名男女正常供体的口腔黏膜三个不同部位（颊黏膜、舌侧缘和口底）获取打孔活检标本（n = 60）。经过甲醛固定和石蜡包埋后，采用免疫组织化学方法检测增殖标志物Mib-1、细胞周期蛋白D1和着丝粒相关蛋白CENP-F。对三种标志物染色切片的分析显示出相似的模式，即在所有三个口腔内部位，基底层的标记指数（LI）较低，副基底层的LI较高。在副基底层以上（表层）未见增殖活性。所有部位增殖标志物的Mib-1 LI值相似。舌上皮的细胞周期蛋白D1和CENP-F副基底层LI高于其他两个部位。吸烟者和非吸烟者之间未检测到显著差异。将正常黏膜的数据与低级别（n = 30）和高级别（n = 17）发育异常白斑的数据进行比较。Mib-1 LI显示出非常显著的变化，发育异常白斑的基底层LI增加了9倍。细胞周期蛋白D1和CENP-F显示出相似的趋势，高级别发育异常的基底层增加高达7倍。尽管正常和白斑上皮的副基底层增殖活性相似，但表层的增殖活性主要在高级别白斑中显著增加。这些研究表明，癌前病变基底层和表层细胞中的增殖标志物可能作为化学预防试验的替代终点生物标志物。
