The Relationship Between Cell Proliferation And Apoptosis Of Nasopharyngeal Carcinoma And Radiosensitivity

Radiotherapy is one of the general medical treatment methods of tumor clinically nowadays. However there are notable different therapeutic effects in different patients in all kinds of tumors even in the same kind of tumor. Inherent radiosensitivity of tumor cell is one of critical factors among all kinds of the factors affecting the radiotherapy effect. According to World Health Organization (WHO) rough estimation, about 80% nasopharyngeal carcinoma (NPC) worldwide occur in China and occur in Guangdong most frequently. Radiotherapy is the major treatment method of NPC. But patients may have different radiosensitivity and radiotherapy effect even the patients have the same pathological classification, clinical stage and the dose and mode of treatment clinically. Although the affective factors of the radiosensitivity of NPC are multifarious, cell proliferative activity and cell apoptosis are the important factors undoubtedly among them. If we could find out the biomarkers of cellproliferation and apoptosis which correlate with the radiosensitivity of NPC, we would be able to predict the level of the radiosensitivity so that the radiotherapeutic scheme and radiotherapy effect of each NPC patient would be specifically improved. In this study, we investigate the relationship between PCNA , P53 protein, DNA content and MI which were biomarkers of cell proliferation and radiosensitivity of NPC.The relationship between SAI, Bcl-2, Bax proteins and Bcl-2/Bax ratio which were biomarkers of cell apoptosis and radiosensitivity of NPC was also investigated so as to find out the biomarkers for predicting the radiosensitivity of NPC.Methods1. Objective: 51 paraffin embedded specimens of NPC were selected from the Department of Pathology, Shantou University Medical School in the period from May 1997 to December 2001.2, HE staining: Histopathological diagnosis was made and mitotic index was counted under microscopy.3, immunohistochemical method: The expression of PCNA , P53 ,Bd-2 and Bax proteins was detected by En Vision method in 51 biopsy specimens prior to radiotherapy of NPC.4. TUNEL method: Spontaneous apoptosis in 51 biopsy specimens prior to radiotherapy of NPC was detected and spontaneous apoptosis index(SAI) was demonstrated.5, Image analysis: DNA content and nuclear morphologic parameters were evaluated.ResultL Histopathological diagnosis: The tumour histology of 51 NPC patients was classified into three distinct groups of type I (keratinizing squamous cell carcinoma) (n=3), type II (non-keratinizing differentiated carcinomas)(n=30) and type III (undifferentiated carcinoma) (n=18) according to World Health Organization (WHO) classification. 2. The factors of cell proliferation(1) The expression of PCNA and P53 protein: The positive expression rates of PCNA and P53 protein were 98.0% (50/51) and in 90.2% (46/51) respectively. The high expression rates of PCNA and P53 protein were 31.4% (15/51) and in 43.1% (18/51) respectively. The expression between PCNA and P53 protein were highly correlated (P<0.01) . The difference was not significant (P>0.05) among keratinizing squamous cell carcinoma, non-keratinizing differentiated carcinomas and undifferentiated carcinoma in relation to the expression of PCNA or P53 protein. The difference of PCNA or P53 protein expression was not significant (P>0.05) among T stages, N stages and stage II, stage III and stage IV. The higher positive expressions PCNA and P53 proteinwas, the higher radiosensitivity was and the better curative effect of NPC was (P<0.05). Furthermore the higher radiosensitivity of NPC was found in the cases with higher positive expressions in both PCNA and P53 protein rather than in those with either PCNA or P53 protein high expression (P0.05) . There was no significant difference (P>0.05) in the 3-year survival rate between the PCNA(or P53 protein) high expression group and the PCNA (or P53 protein) low expression group with chi-square analysis and Kaplan-Meier method.(2) DNA content and nuclear morphologic parameters: In...