The Study Of Survivin, P21～(WAF1/CIP1), CyclinD1 Gene Protein Expression In Cervical Carcinoma: Correlations With Recurrence Of Ia-IIb Stage Cervical Cancer Of The Uterus

ObjectiveTo study the expression of Survivin, P21WAF1/CIP1 and CyclinDl proteins in cervical carcinoma and to investigate their relation with recurrence of Ia ~ IIb stage cervical cancer of the uterus.MethodsUsing streptavidin - biotin peroxidase ( sp ) method, we examinedthe protein expression ot survivm, p21 and cyclmUl proteins in55 cervical carcinomas (45 cervical squamous carcinomas and 10 cervical adenocarcinomas ) and 10 normal cervical tissues.Results1. Survivin was expressed in 31 of 45 cases of cervical squamous carcinomas (68. 9% )and in 6 of lOof cervical adenocarcinomas (60. 0%). In contrast, normal cervical epithelium did not express sur-vivin. P21WAF1/CIP1was expressed in 26 of 45 cases of cervical squamous carcinomas (57. 8% ) and in 8of 10 cases of cervical adenocarcinomas (80%) and1 of 10 normal cervical tissues ( 10% ). Cy-clinD1was expressed in 23 of 45 cases of cervical squamous carcinomas (51. 1% ) and in 9 of 10 cervical adenocarcinomas(90% ) and in 1 of lOcases of normal cervical tissues(10% ). The expression of sur-vivin, p21WAF1/CIP1and cyclinDl in cervical carcinoma all had significant difference from normal cervical tissue (P <0. 05) .2. Positive expression of survivin and cyclinDl were associated with higher tumor grade and clinical stage (P < 0. 05 ). Positive expression of p21WAF1/CIP1 Was not related to clinicopathologic features (P>0.05).3. The coexpression of Survivin/ P21WAF1/CIP1/cyclinDl and any both coexpression were associated with higher tumor grade ( P < 0. 05) , While the coexpression of Survivin/cyclinDl was related to higher clinical stage(P < 0. 05).4. Positive expression of Survivin and cyclinDl all were related to recurrence of Ia ~ IIb stage cervical cancer ( P <0. 05) . The coexpression of Survivin /cyclinDl were associated with the pelvic lymph node metastasis and recurrence of Ia ~ IIb stage cervical cancer ( P < 0.05).DiscussionSurvivin is a novel strong inhibitor of apoptosis protein . Apoptosis pathways mainly are effectively blocked by survivin directly/indirectly inhibiting cysteine proteasecysteine protease caspase - 3 and caspase -7. The study in vitro have shown that pathway of antiapoptosis of survivin protein is interaction with survivin and Cdk4 that release p21w clp from the Cdk4/p21 complex and reduces formations of pre-capase3/p21 complex . Survivin is undetectable in normal adult tis-sues, yet it is abundantly expressed in fetal tissue and in a variety of human tumors . This selectively enhanced expression of survivin in tumor to show that tumor cells are able to switch on survivin gene and get out of apoptosis and abnormal proliferation. The result of experiment was that normal cervical tissues did not express survivin . yet cervical squamous carcinomas and adenocarcinomas high expressed survivin. It shows that survivin may play an important role in cervical carcinoma occurrencing and developing . Survivin high expressed in higher tumor grade and clinical stage, and was related to recurrence of Ia ~ IIb stage cervical cancer . Positive expression of survivin in 5 recurrent cases showed that survivin protein expression was strongly correlated with incursions and poor prognosis of cervical carcinomas. Cy-clindl is Glstage cyclin protein.,and it is able to switch Glto S phase and to accelerate the synthesis of protein and cell proliferation, Many investigators have reported correlation between cyclinDl expression and prognosis in lymphoma, prostate, thyroid cancer. In this experiment, cyclindl expression was increased in cervical cancer and was associated with higher clinical stage and higher tumor grade of squamous carcinoma, and unfavorable prognosis of Ia ~ IIb stage cervical cancer . Positive expression of cyclindl in 5 recurrent cases showed that cyclindl protein expression was strongly correlated with incursion and poor prognosis of cervical carcinoma. While the p21wafl/cipl is anti - on-cogene . It inactivates the cyclin/cdk complexes blocking the cell cycle progression in the Gl -...