The Clinical Significance Of Smad₄ And P～(21ras) Expression In Pancreatic And Ampullar Carcinoma

Background: DPC4 gene is an anti-oncogene, K-ras is an oncogene, both of them are specific markers to pancreatic carcinoma, and their products are2 ras protein Smad4 and P Objective: To investigate the expression of anti-oncogene product Smad4 and oncogene product P2lras in pancreatic carcinoma and periampullar carcinoma, and the relationship of them to the clinic pathological characteratics; to elucidate the role of the two proteins expression on the differential diagnosis of pancreatic carcinoma and periampullar carcinoma. Methods: 67 paraffin-embedded and pathologically proved specimens including pancreatic carcinoma (n=22), periampullar carcinoma (n=1 5), lymph node with pancreatic carcinoma metastasis (n9), benign disease of pancreas (n=1 8) and normal pancreas (m=3) were immunohistochemically stained with monoclonal primary antibodies of Smad4 and p2lras respectively by using the EnVision system. Results: Loss of Smad4 was detected in II specimens of 22 pancreatic carcinomas (50.00%), 2 of 15 periampullar carcinomas (13.33%), 4 of 9 lymph nodes with pancreatic carcinoma metastasis (44.44%), 3 of 18 benign diseases of pancreas (16.67%), 3 of 13 chronic pancreatitis (23.08%) and none of 3 normal pancreata (0.00%). The positive2lras expression rate of P was 77.27% in pancreatic carcinomas (17/22), 26.67% in periampullar carcinomas (4/15), 44.44% in lymph nodes with pancreatic carcinoma metastasis (4/9), 3 8.89% in benign diseases of pancreas (7/18), 38.46% in chronic pancreatitis (5/13) and none in normal pancreata (0/3) respectively. The loss of Smad4 showed significant difference in pancreatic carcinoma and periampullar carcinoma as compared to benign disease of pancreas (p <0.05) , so did the positive expression 0fp2lraS (p <0.05) . The loss of Smad4 was not significant related to the age, sex, symptom, tumor size, tumor site, pathological degree, clinical stages and lymph node metastasis (p >0.05) ,. and neither was the expression of p2lras (p >0.05) . Loss of Smad4 was not related to the expression 0fp2lras in each disease (p >0.05) ,just as reported in other carcinomas. Conclusions: Immunohistochemical labeling for theSmad4 and P2lras has been shown to be an extremely sensitive and specific method fordetecting the DPC4 and K-ras alterations in pancreatic carcinoma. To detect DPC4 andK-ras gene expression could be helpful in the differential diagnosis amongpancreatic carcinoma, periampullar carcinoma and the benign diseases. The K-rasgene occurs early in the carcinogenesis of pancreatic carcinoma, and thereafter theloss of DPC# plays a very important role in the progress of pancreatic carcinoma.