Ohbu M, Kobayashi N, Okayasu I
Department of Pathology, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Sagamihara, Kanagawa, 228-8555, Japan.
Histopathology. 2001 Dec;39(6):589-96. doi: 10.1046/j.1365-2559.2001.01279.x.
Cell cycle regulatory proteins were analysed by immunohistochemistry in order to clarify how their expression changes with the degree of atypia as oesophageal surface squamous epithelium progresses from normal mucosa, through reactive change, low-grade dysplasia, and high-grade dysplasia to mucosal invasive carcinoma.
Immunostaining for cyclin D1, cyclin E, p21, p27, p53 and Ki67 proteins was performed using 22 normal mucosa, 17 reactive change, 22 low-grade dysplasia, 15 high-grade dysplasia and 22 mucosal invasive carcinoma specimens. Normal mucosa, low-grade dysplasia and high-grade dysplasia samples were taken from patients without any oesophageal invasive carcinoma by endoscopic biopsy or endoscopic mucosal resection, and reactive change and mucosal invasive carcinoma were obtained from oesophagectomy material. Stepwise over-expression of cyclin E (P < 0.0001) and p53 (P < 0.0001), reduction of p21 (P=0.0189) and dysregulation of cyclin D1 and p27 were observed in the multistep process of oesophageal carcinogenesis. Significant differences in expression of p27 (P < 0.0001), p53 (P=0.0299) and Ki67 (P=0.0101) were observed between reactive change and low-grade dysplasia. Furthermore, expression of cyclin D1, cyclin E, p27 and p53 in mucosal invasive carcinoma were significantly different from those in high-grade dysplasia (P=0.0079, P=0.0237, P=0.0042 and P= 0.0299, respectively).
Cell cycle regulatory proteins, cyclin E, p53 and p21 show stepwise over-expression or reduction with progression of oesophageal carcinogenesis, correlating with the increased cell proliferation observed with Ki67 labelling. We conclude that immunohistochemical analysis for p27, p53 and Ki67 is practically useful for the discrimination between low-grade dysplasia and reactive change. Cyclin D1, cyclin E, p27 and p53 help to distinguish high-grade dysplasia from mucosal invasive carcinoma.
通过免疫组织化学分析细胞周期调节蛋白，以阐明随着食管表面鳞状上皮从正常黏膜，经反应性改变、低级别异型增生、高级别异型增生发展至黏膜浸润癌，其表达如何随异型程度变化。
使用22例正常黏膜、17例反应性改变、22例低级别异型增生、15例高级别异型增生及22例黏膜浸润癌标本进行细胞周期蛋白D1、细胞周期蛋白E、p21、p27、p53和Ki67蛋白的免疫染色。正常黏膜、低级别异型增生和高级别异型增生样本取自未经食管浸润癌的患者，通过内镜活检或内镜黏膜切除术获取，反应性改变和黏膜浸润癌样本取自食管切除术材料。在食管癌发生的多步骤过程中，观察到细胞周期蛋白E（P < 0.0001）和p53（P < 0.0001）逐步过度表达，p21减少（P = 0.0189），细胞周期蛋白D1和p27失调。在反应性改变和低级别异型增生之间观察到p27（P < 0.0001）、p53（P = 0.0299）和Ki67（P = 0.0101）表达的显著差异。此外，黏膜浸润癌中细胞周期蛋白D1、细胞周期蛋白E、p27和p53的表达与高级别异型增生中的表达显著不同（分别为P = 0.0079、P = 0.0237、P = 0.0042和P = 0.0299）。
细胞周期调节蛋白细胞周期蛋白E、p53和p21随着食管癌发生进展呈现逐步过度表达或减少，与Ki67标记显示的细胞增殖增加相关。我们得出结论，p27、p53和Ki67的免疫组织化学分析对于区分低级别异型增生和反应性改变具有实际应用价值。细胞周期蛋白D1、细胞周期蛋白E、p27和p有助于区分高级别异型增生与黏膜浸润癌。
