| IntroductionHie retinoblastoma ( Rb) is a malignant tumor arises from retina. In recent studies the abnormal Rb gene has been found in several human neoplasms including osteosarcoma, lung cancer, breast cancer, bladder carcinoma and carcinoma of prostate, which indicated that Rb was one of the most important tumor suppressor genes in human body.The Rb gene is localized to human chromosomel3ql4 and encode a 105kd protein. The combination of pRb and the transcription factor E2F can suppress the expressions of E2F - dependent proliferation - associated molecules and control the cell proliferation. The low phosphorylation of pRb is in its active state liable to combine with E2F, leading to the arrest of cell cycle at Gl phase. After the transmission of proliferation signal into the cell pRb is phosphorylated by cy-clin D/CDK4/6 complexes and changed into the highly phosphorylated form in which loses the ability of binding to E2F. The free E2F then acts as a transcription activated factor and permits the cell to go into the S phase from Gl phase. The complexes of cyclinD/CDK4 (or CDK6) and cyclinE/CDK2 are the major kinases leading the cell cycle dependent phosphorylation of pRb. Recent studies have found that p16 and p21, the specific suppressors of cyclin/CDK4/6, can regulate the phosphorylation of pRb and control the cell cycle progression through p16 - cyclm/CDK - Rb and p53 - p21 - cyclin/CDK - Rb pathway.The relationship between the Rb gene family and carcinoma has been demonstrated in previous studies. The Rb abnormality was observed in 20% of malignant tumors, and the disruptions of p16 - cyclin/CDK - Rb or p53 - p21 -cyclin/CDK - Rb pathway were in 80%. The Rb gene abnormality was one of the hereditary factors associated with the occurrence of lung cancer, and the abnormal Rb gene was found in 90% of small cell lung cancer (SCLC) and 10 -30% of non - small cell lung cancer ( NSCLC). pRb correlated well with the prognostic evaluation of SCLC such as malignant degree, clinical stage and lymph node metastasis. But in NSCLC there is no final conclusion. In recent years the new members of Rb gene family, p107 and Rb2/pl30 have been found, which are functionally similar to pRb but they are not entirely substitulive each other. There is rare study about the role of Rb2/pl30 in NSCLC, and the major results are derived from the Claudio study group. They detected the pRb, p107 and Rb2/pl30 in lung cancer specimens with immunohistochemical method and found the lower expressions of these three proteins which correlated with the progression and staging of lung cancer. Furthermore, they detected the gene mutation in 14 specimens with SSCP analysis and found the mutated Rb2/pl30 in 12 specimens. But in NSCLC it is not clear about the disruption of p53 - p21- cycli/CDK - Rb and pi6 - cyclin/CDK - Rb pathway, especially about the correlation of the abnormality of Rb and its family with the prognosis. TTie present study is to investigate the relationships between the alternations of Rb, p16, p53, p21, especially the Rb2/pl30 and prognosis in NSCLC.Materials and methodsClinical informationEighty - seven patients with lung cancer underwent surgical operations were diagnosed through histopathological examination. , and the pathological stage was determined based on the ICCU criteria. The observation periods ranged from 3 to 123 months ( median follow - up period: 41.5 months).Histopathological examination and Immunohistochemistry. Hie surgically resected tumor tissues and normal lung tissues were fixed in 10% neutral formalin and embedded in paraffin. All 4 uM sections were stained with hematoxylin- eosin(HE) and underwent pathological diagnosis and classification. All sections then were deparaffinized in xylene, rehydrated through a graded alcohol series , and heated at 92 - 98 C to restore the antigen.. Tissue sections were sequentially immersed in 0.3% hydrogen peroxide/methanol to block endogenous peroxidase activity and blocked with diluted 10% normal goat anti - rabbit ser-tun ( DA...
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