The Expression And Clinical Significance Of PTEN,P27,TGF-β₁ In Cervical Adenocarcinoma

Objective :Cervical cancer is one of the main course of women death, and the morbidity age become more and more younger in recent years, especially the raised morbidity of cervical adenocarcinoma. It's said by researches that the originate and development of tumor is involved in the activation of oncogene and deactivation of anti-oncogene. The anti-oncogene PTEN, P27 and transfer growth factor TGF-β1 are important in cellular proliferation, differentiation and apoptosis, but it's relatively less reported in adenocarcinoma, and no report was found about the relationship of them. Through immunohistochemistry(IHC), this study determined the expression of PTEN, P27, TGF-β1 in different clinical phases and pathologic characteristics of the cervical adenocarcinoma, to discuss the applicable significance of their in the diagnosis and treatment of adenocarcinoma, meanwhile, to discuss the different of the originate mechanism between cervical squamous carcinoma and cervical adenocarcinoma from cellular factor regulate level. Through this study, a new diagnosis index and a new target for genetic therapy probablely could be established, which could be helpful for elevating the diagnosis level of adenocarcinoma and prognosis judgement .Methods:Expression of PTEN,P27 and TGF-β1 were detected by immunohistochemical staining in 51 cases of cervical adenocarcinoma, 18 cases of normal cervix.Adopt IHC SP,the main stain steps referred to the specifications of the reagent boxes,antigen restored adopted boiling (PTEN/P27) or microwave reparation (TGF-β1). Contrasted by known positive slices(carcinoma of the breast). The primary antibody was substituted by PBS solution for negative contrast.Results:1.The expression of PTEN,P27,TGF-β1 in normal cervix and Cervical adenocarcinoma: PTEN was mainly expressed as light browning or browning granule in cytoplasm,1 case was expressed in nuclear. Among 51 cases of adenocarcinoma,31 cases was PTEN stained positively in different degree,the positive rate was 60.78%,which was significantly lower than that in normal cervix(88.89%,16/18) (P<0.05),and the positive rate in nuclear(3.23%,1/31) was significantly lower than that in normal cervix(56.25%,9/16)( P<0.005). The P27 was expressed mainly in nuclear,as light browning or browning granule also,the positive rate was 50.98% in cervical adenocarcinoma (26/51),which was significantly lower than that in normal cervix (94.44%,17/18) (P<0.05). In normal cervix tissue,the P27 expressed positively as nuclear staining,the cells were well-distribute each level. In cervical adenocarcinoma tissue,P27 was partly positively expressed in cytoplasm(38.46%,10/26),the positive cells distributed disorderly,focally distributed in sight. TGF-β1 positive granules were browning, mainly located at cytoplasm of tumor cells,expressed as diffused or focally distributed. TGF-β1 was positive expressed in normal cervix at the percent of 11.11% (2/18). Among 51 cases of adenocarcinoma,only 2 cases of poorly differentiated adenocarcinoma of endometrial type and 1 moderately differentiated adenocarcinoma of endometrial type expressed positively (5.88%),the others were negative all. The positive rate of TGF-β1 has no significant difference in normal cervix and in cervical adenocarcinoma (P>0.05).2.the relationship between the expression of PTEN,P27,TGF-β1 in cervical adenocarcinoma and the clinical or pathological characteristics: There was no relationship between the expression of PTEN,P27,TGF-β1 in cervical adenocarcinoma and the patients'ages(P>0.05). The level of PTEN or P27 expression in cervical adenocarcinoma decreased when clinical stage increased (P<0.01). The expression of PTEN or P27 was in high level in well differentiated carcinoma tissue , compared with intermediate or low differentiated carcinoma tissue,but no difference in low and intermediate differentiated ones (P>0.05). The level of P27 was significantly lower in clear cell adenocarcinoma and adenosquamous carcinoma than in other types of carcinoma (P<0.05). There was no relationship between the expression of TGF-β1 in cervical adenocarcinoma and the characteristic of clinical or pathology (P>0.05). The expression of PTEN was positively correlated with P27 in cervical adenocarcinoma (r=0.8082,P<0.001). No relationship was found between TGF-β1 and PTEN or P27 ( rPTEN=0.026,P>0.05;rP27=0.021,P>0.05 ).Conclusion:1.Inactivation of PTEN and deficiency of P27 protein were involved in the origin and development of cervical adenocarcinoma, and were related to the differentiation of cancer cell. Inactivation of PTEN and deficiency of P27 protein maybe led to the poor cellular differentiation, and high malignancy.2.There was a positive correlation between the expression of PTEN and of P27, suggested that PTEN may affect the cellular regulate factor such as P27 to participate in the origin of cervical adenocarcinoma.3.The level of PTEN or P27 expression in cervical adenocarcinoma was decreasing went with the increasing of clinical stage (P<0.01), which implied that the detection of PTEN and P27 could be available in the prognosis of cervical adenocarcinoma.4.The function link of the PTEN, which led a anti-tumor in adenocarcinoma, maybe in the nuclear, and need advanced study on the mechanism.5. PTEN, P27 could be regarded as the target of genetic therapy in clinic. To elevate the expression of PTEN, P27 maybe beneficial to the therapy and prognosis of cervical adenocarcinoma.6. TGF-β1 expression abnormally may not act as a chief factor in the origin and development in cervical adenocarcinoma, but its positive expression was correlated to the histological grade, it was relatively higher expressed in low differentiated adnocarcinoma, and need more confirmation by lage-sample theory.7. Regarding the anti-tumor function of the PTEN, there could be some commoness of the originated mechanism in cervical squamous carcinoma and adenocarcinoma;but it was maybe different that the anti-tumor mechanism of P27 between cervical squamous carcinoma and adenocarcinoma. The cervical squamous carcinoma origination were related to the P27 sub-cell location, but it was not so regarding to the cervical adenocarcinoma.8. The pathogeny between cervical squamous carcinoma and cervical adenocarcinoma was possibly different. There could be some difference of cellular regulate factors such as TGF-β1 between the cervical squamous carcinoma and cervical adnocarcinoma.