The Expression And Clinical Significance Of P27～(kip1) In Ovarian Tumor

Objective: Ovarian carcinoma is one of the most commonmalignant tumor of the female gential tract and seriously threats femalehealth. There exists increase trend in ovarian carcinoma incidence inrecent 20 years, however, its onset mechanism is not clear. It wasreported that P27Kip1 factor was closely associated with the incidence,infiltration and metastasis of ovarian carcinoma. Polyak et al (1994)applied TGF and contact inhibition to MV1LU cells and found a proteinof molecular weight 27 KD from cell extract protein and nominated it byP27Kip1. P27Kip1 functions at the nuclear level by binding to cyclin Cdkcomplex. It has been shown to block the progression from G1 to Sphase by inhibiting the activity of cyclin Cdk complex and suppress cellgrowth. In the human and rats, there have two serine phosphorylatedsections in the N-terminal of P27Kip1, which inhibit the activity of Cdkkinase; a threonine phosphorylated section in the C-terminal of P27Kip1,which associated with inhibiting the phosphorylated H1 protein.P27Kip1 can inhibit cells mitosis and proliferation, meanwhile, promotecells differentiation and apoptosis, so P27Kip1 has close relation with theincidence, development, diagnosis, and therapy of carcinomas. It wasshowed that P27Kip1 expression decreased in uterus carcinoma ofendometrium compared with P27Kip1 expression in normal proliferousstage of endometrium, simple hyperplasia endometrium and combinedhyperplasia endometrium, which suggested that P27Kip1expressionwere related with uterus carcinoma of endometrium. P27Kip1expressionis frequently reduced in cancers including alimentary system,cephalo-cervial carcinoma, and skeletal and smooth muscle sarcomas,and leukemia. In previous studies, the literatures about the relationbetween P27Kip1 expression and incidence, infiltration and metastasis ofovarian carcinoma were rare. This study was to observe the level ofP27Kip1 expression in benign and malignant tumor and expressionchanges in differential cancer stage and exacerbation companied withlymphatic metastasis and ascites in order to provide theory basis for theinfiltration, metastasis and treatment of ovarian carcinoma. Methods: The samples were chose from the Second ClinicalHospital of Jilin University from 1995 to 2000. 15 benign tumor samplesfrom patients who underwent surgery of unilateral oophorectomy wereused. 45 epithelial ovarian cancer samples were out of patients whounderwent oophoroma radical operation without chemotherapy andradiotherapy before surgery. According to the FIGO standard, Ⅰstageincluding 10 samples, Ⅱstage including 14 samples, Ⅲstageincluding 14 samples, Ⅳstage including 7 samples, among them 27samples with lymphatic metastasis, 18 sample without lymphaticmetastasis. Immunohistochemical detection for subcellular localizationof P27Kip1 was performed using SP detection kit. 5 micrometer sectionsof archival paraffin-embedded blocks were cut, deparaffinized, andstained using a streptavidin-biotin immunoperoxidase techniques. The Immunohistochemical staining was evaluated by visualcounting of cells from at least 10 random high-power fields (100×) witha minimum of 1000 cells counted by three authors. A grading systembased on the percentage of cells that exhibit any staining was used. If1-25% of cells were positive, a score of low staining was assigned 1. Amoderate staining designation 2 was noted if 26-50% of cells werepositive; high 3 if 51-75% were positive, and very high 4 if more than75% of cells stained positive. The Immunohistochemical staining alsowere graded by color. Light yellow was noted 1, brown was noted 2,heave brown 3. The two analysis score was multiplied. The result 0-1was assigned (-);if 2-3 of the result was assign low positive(+);moderate positive (++) if the multiply was 4-5; strong positive (+++) ifthe result was more than 5. Immunohistochemical results wereanalyzed with SPSS 10.0 Statistical soft. The analysis was performedusing analysis of variance and χ2 test. Results: P27Kip1 protein was observed both in ovarian benign andmalignant tumor. The expression of P27 Kip1was higher in ovarianbenign tumor than that in malignant tumor (P<0.01). The lowerexpression of P27 Kip1were observer in the poor and moderatedifferential of OEC than that in well differential OEC (P<0.01); however,there is not obvious significance between the poor and moderatedifferential OEC (P>0.05). The expression of P27 Kip1 was higher in theearly OEC (clinical Ⅰ,Ⅱstage) than that in advanced OEC(clinical eⅢ,Ⅳstage) (P<0.05). Concludes: The P27 Kip1 has close relationship with malignantdegree of tumor. The poorer differentiation was observes in tissuecompanied with the more highly malignant degree and the higher rateof lymphatic metastasis, so P27 Kip1 probably is the important factor that...