p53-p21waf1通路在口腔鳞状细胞癌中心体扩增中的作用及意义

目的 了解口腔鳞状细胞癌(oral squamous cell cancer,OSCC)p21waf1蛋白表达与中心体扩增的相关性,探讨p53-p21waf1通路在OSCC中心体扩增中的作用及意义.方法 8例正常口腔黏膜及27例OSCC石蜡包埋组织,采用间接免疫荧光双重染色法了解OSCC组织中心体扩增情况;采用流式细胞术及免疫组织化学方法对相应组织p21waf1蛋白表达量及突变型p53蛋白进行检测,分析三者间的相关性.结果 中心体数目扩增(＞2个/细胞)可见于78%(21/27)的OSCC组织,p21waf1蛋白表达量在有中心体扩增的OSCC组织中(0.878±0.081)]低于无中心体扩增的OSCC组织(0.952±0.018),t=3.838,P=0.001],OSCC组织中心体扩增程度与p21waf1蛋白表达量间存在负相关关系(r=0.472,P＜0.05);p21waf1蛋白表达量在OSCC组织p53阳性组(0.823±0.071)]低于p53阴性组(0.909±0.075),t=3.905,P＜0.01],两者间存在负相关关系(r=-0.491,P＜0.05).结论 p53-p21waf1通路可能参与了OSCC中心体循环调控,p53突变导致的p21waf1蛋白表达下调在OSCC中心体扩增中可能起一定作用.

The p53-p21waf1 pathway and centrosome amplification in oral squamous cell carcinomas

Objective To elucidate the possible role of p53-p21waf1 pathway for centrosome amplification in oral squamous cell carcinoma ( OSCC ) . Methods Formalin-fixed, paraffin-embedded tissues of 8 cases of normal oral epithelium tissues and 27 cases of OSCC tissues were examined for the expression of p21waf1 and mutated p53 proteins by flowcytometry and immunohistochemistry, and centrosome status was investigated by indirect immunofluorescence double staining with antibodies to centrosome protein gamma-tubulin and cytokeratin. The correlation between p21waf1, p53 and centrosome amplification in OSCC was statistically analyzed by SPSS 12.0. Results All normal oral epithelium tissues showed normal centrosomes( 1-2 centrosomes per cell) in epithelium cells, while 21 out of 27 cases(78%) of OSCC showed the evidence of centrosome amplification characterized by supernumerary centrosomes (＞2 centrosomes per cell) in a fraction of tumor cells. The quantity of p21waf1 protein was lower in OSCC with centrosome amplification (0. 878±0. 081 )] than that in OSCC without centrosome amplification (0. 952±0. 018 ) ,t =3.838,P<0.01] , and negative correlations were found between the quantity of p21waf1 protein and the degree of centrosome amplification ( r = - 0.472, P＜0. 05) , as well as the positive staining of p53 ( r =-0.491 ,P＜0. 01). Conclusions p53-p21waf1 pathway might involve in centrosome duplication cycle in OSCC. Down-regulated p21waf1 protein, via p53 transactivation-dependent mechanism, was likely a contributing factor towards centrosome amplification in OSCC.