Expression Of P53, P21～(WAF1), PCNA In Nephroblastoma And Its Clinical Significance

Backgrounds Nephroblastoma is one of the most common abdominal malignant tumor in children, especially aged from 2 to 5, It is about 6% of children's malignant tumor, and the ratio between male and female is 1.3 to 1.Nephroblastoma generates from metanephric blastema in embryogenesis and offen occurs with congenital malformation, such as congenital lacking of iris, malformation of urinary and reproductive system or mental deficiency. Many gene mutations (for the pathogenesis of nephroblastoma ) have been identified, and these genetic changes are early molecule events in the multistep genetic pathogenesis of nephroblastoma. Nowadays its main prognosis factors are the histopathological type, age, clinical tumor stage, and clinical comprehensive therapy. There is no specific tumor marker in nephroblastoma now.Cell cycle is the basic course of cell activity, normal cell undertakesaccurately DNA reproduction on S stage and equally distributes DNA into two daughter cells to finish cell proliferation. During this course, there are two important check points: Gi/S and G2/M, which are regulated by many genes. If these genes express abnormally, especially negative regulating genes, the function of check point will lose or decrease, which contributes to the tumorigenesis finally. Wild type p53 gene or protein takes an important role in the course of monitoring and negatively regulation of cell proliferation cycle. The signal of mutation or damage of DNA, which can induce p21WAF1 transcription andtranslation, can be transferred to wild-type p53. p21WAF1 is a common inhibitor of cell cycle. One hand, it can directly inhibit the driving function of cyclin-CDK on cell cycle; on the other hand, p21WAF1 can conjugate and inhibit PCNA, which can speeds up DNA reproduction and is a cell proliferation marker .By means of immunohistochemical techniques, the p53 , PCNA and p21WAF1 expression were detected in nephroblastoma. Their mutual relationships and influence on cell proliferation cycle were investigated and their practical value in the prognosis and diagnosis in nephroblastoma were evaluated.Materials and Methods 32 children's nephroblastoma (tumor group) and 7 benign nephridium tissue (control group) from surgical resections were collected, and all the sections were formalin-fixed and paraffin-embedded. The patient, from 10 months to 13 years, average 3.47 1.80 years, 18 males and 14 females, were not performed with any radiotherapy and chemotherapy. HE staining of all the sections were affirmed and the histopathologic types were classified according to the conditions during operation and the pathologic diagnosis after operation ( by NWT-3 criteria ). Among them 7 patients were stage 1,14 stage II , 8 stage III and 3 stage IV; 25 patients were FH (favorable histology ) type tumor, 7 UH (unfavorable histology ) type. p53, p21WAF1 and PCNA expression were detected by immunohistochemistry. The positive rate of p53 expression, . PCI and PI represent the level of p53, PCNA and p21WAF1 expression status respectively. The results were analyzed using SPSS 10.0 statistical software.Results (1) The positive rate of p53 was 21.9% in tumor group (7/32), while all negative in the control group. Statistical analysis showed there was no significant difference in the expression of p53 between tumor group and control group; PCI was higher in tumor group than that in control group (46.53% 22.13% / 16.00% 12.11%) (P < 0.01); PI was higher in tumor group than that in control group (46.44% 23. 58% / 3.57% 3.95%) (P < 0.001). (2) The positive rate of p53 was lower in FH type than that in UH type (8.0% / 62.5%) (P < 0.01), PCI was lower in FH type than that iri UH type (41. 56% 19.54% / 64.29% 23.06%) (P < 0.05); PI was higher in FH type than that in UH type(53.28% 20.56% / 22.00% 17.04%) (P < 0.01). (3) The positive rate of p53 was lower in I -II stage than that in HI~IV stage (9.5% / 45.5%) (P < 0.05); PCI was lower in I -II stage than that in III-IV stage(39.19% 20.10% / 60.55% 19.52%)(P<0.01); PI was...