The Expression Of Fhit Protein And Its Relationship With Bax/Bcl-2 Proteins In Pancreatic Carcinomas

background: FHIT gene, which is a novel tumor suppressor gene , is frequently abnormal in many cancers including pancreatic carcinoma. And its product is Fhit protein.Objection: 1. To investigate the correlation of FHITmRNA and the expression of Fhit protein in pancreatic carcinoma.2. To study the expression of Fhit protein in pancreatic carcinoma, and the relation to the clinicpathological characteratics.3. To study the expression of Bax/Bcl-2 protein in pancreatic carcinoma,and explore the effect of them and the expression of Fhit protein in the process of pancreatic carcinoma.Methods: FHITmRNA was checked by RT-PCR in 8 cases fresh pancreatic carcinoma. 62 paraflin-embedded and pathologically proved specimens including pancreatic carcinoma and corresponding adjacent noncarcinoma tissue (n=38), benign disease of pancreas (n=20), normal pancreas (n=4) were immunohistochemically stained with polyclonal primary antibody of Fhit; And pancreatic carcinoma (n=38) were immunohistochemically stained with monoclonal primary antibodys of Bax and Bcl-2 respectively by using the S-P system.Result: Aberrant-sized FHIT transcripts were observed in 5 of 8 cancer tissue by a RT-PCR method. The tumor sections obtained from the same cases showed that 4of 5 with Aberrant-sized FHIT transcripts were observed negative for staining,only one case was postive for staining, whereas all cases with normal-sized FHIT transcripts were observed postive for staining.A good correlation between FHITmRNA alteration and loss of Fhit protein expression. The loss of Fhit protein expression was detect in 21 cases of 38 pancreatic carcinomas(55.28%), 9 of 38 corresponding adjacent noncarcinoma tissue(23.68%) , 4 of 20 benigndisease of pancreas(20.00%) and 0 of 4 normal pancreas. The loss of Fhit protein showed significant difference in pancreatic carcinomas, adjacent noncarcinoma tissue (p<0. 01), benign disease of pancreas(p<0. 05) and normal pancreas(p < 0. 05). Loss of Fhit expression was significantly associated with advanced clinical stages and lymph metastasis(p<0. 05). It was not significantly related to the age, sex, tumor size, tumor site, histological grade and infiltration (p>0. 05). In pancreatic carcinomas with positive Fhit expression, the expression rate of Bax protein was ( 34.2 ±9.3 ) % and was (24.2 ±7.1) % in the cases without expression of Fhit .There was significantly difference between them (p<0. 01). And Fhit expression was not related to the expression rate of Bcl-2 protein in pancreatic carcinomas(p> 0. 05).Conclusions: 1. A good correlation was between FHlTmRNA alteration and loss of Fhit protein expression,and immunohistochemically labeling for Fhit has been shown to be an sensitive and specific method for detecting the FHIT gene aberrant in pancreatic carcinomas.2. Loss of Fhit expression was significantly associated with advanced clinical stages and lymph metastasis .To detect the expression of Fhit in pancreatic carcinomas could be helpful in comprehend clinicopathological of cancers and appears to be a potential prognostic factor .3. Fhit and Bax/Bcl-2 protein take part in the developing of pancreatic carcinomas by adjusting the path of apoptosis , the apoptosis induced by Fhit may be related to Bax protein.