Relationship between p27^<Kip1> expression and tumor differention and prognosis in human oral squamous cell carcinoma.

我们利用免疫组织化学方法研究了p27^<Kip1>在口腔鳞状细胞癌（OSCCs）中的表达，并试图探讨各表达水平与肿瘤分级、T、N、分期、疗效和转归等临床病理特征之间的关系。高水平表达p27^<Kip1>与高分化病例（p<0.05）、NO病例（p<0.01）、非晚期病例（p<0.01）、良效病例（p<0.05）相关。p27^<Kip1>高表达组5年生存率为63.3%，显著高于p27^<Kip1>低表达组（45.5%）（p<0.05）。通过Cox比例风险模型，高水平表达p27^<Kip1>可显著降低死亡率。这些结果提示p27^<Kip1>蛋白表达可能与肿瘤分级、转移抑制、疗效和预后密切相关，是一种有用的预后指标。接下来，我们用pcDNA3.1 （stratagene）构建了p27^<Kip1>表达载体。并将其以正义或反义定向转染到OSCC细胞系（B88）中，试图调控B88细胞中的p27^<Kip1>基因。B88细胞过表达p27^<Kip1> (B88/Tp27sense)可抑制B88细胞的生长、侵袭和转移。相反，B88细胞中p27^<Kip1> （B88/ tp27反义）的低表达促进了B88细胞的生长、侵袭和转移。在肿瘤分化方面，我们可以检测到B88/ tp27反义细胞从鳞状细胞型到spindol细胞型的形态学变化，但HE染色未检测到亲本B88和B88/ tp27的差异。此外，我们可以通过免疫组化检测B88/ tp27感中天合蛋白和角蛋白7,8 （Cam 5.2）的诱导作用。提示p27^<Kip1>可能与OSSC终末分化有关。

We have investigated the expression of p27^<Kip1> in oral squamous cell carcinomas (OSCCs) using immunohistochemistry and have tried to investigate the relationship between each expression level and clinico-pathological characteristics such as tumor grade, T, N, stage classifications, effect and outcome. High levels of p27^<Kip1> expression were significantly related to well differentiated cases(p<0.05), NO cases (p<0.01), non advanced cases (p<0.01), and good effective cases (p<0.05). Five-year survival rate of p27^<Kip1> high expression cases was 63.3%, and it was significantly high than that of p27^<Kip1> low expression cases (45.5%) (p<0.05). By Cox's proportional hazards model, high levels of p27^<Kip1> expression significantly made the rate of death decrease. These results suggested that p27^<Kip1> protein expression may be closely related to tumor grade, inhibition of metastasis, effect and outcome, and an useful prognostic marker. Next, we have constructed p27^<Kip1> expression vectors with pcDNA3.1 (stratagene). Moreover, we transfected them to OSCC cell line (B88) in sense or anti-sense oriented, and tried to regulate the p27^<Kip1> gene in B88 cells. Overexpression of p27^<Kip1> in B88 cells (B88/Tp27sense) inhibited the growth, invasion and metastasis of them. Contradictory, low expression of p27^<Kip1> in B88 cells (B88/Tp27anti-sense) promoted the growth, invasion and metastasis. On tumor differentiation, we could detect the morphological change from squamous cell type to spindol cell type in B88/Tp27anti-sense though we could not detect the difference between parental B88 and B88/Tp27sense by HE staining. Moreover, we could detect the induction of involucrin and keratin 7,8 (Cam 5.2) in B88/Tp27sense immunohistochemically. These results suggested that p27^<Kip1> might be related to terminal differentiation of OSSC.