Immunohistochemically Detected Expression of Three Major Genes (CDKN2A/p16,TP53 and SMAD4/DPC4) Strongly Predicts Survival in Patients with Pancreatic Cancer
Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Date (from‐to) : 2012/04 -2015/03
Author : OSHIMA Minoru; YACHIDA Shinichi; OKANO Keiichi; SUZUKI Yasuyuki
The pancreatic ductal adenocarcinoma (PDAC) contains 4 frequently mutated genes (KRAS, TP53, p16, SMAD4). We determined the status of TP53, p16, SMAD4 since the KRAS gene is mutated in virtually all PDAC patients, and analyzed relationships with clinicopathological findings in 106 surgical patients with PDAC .
Abnormal of p53 (81%) was associated with the presence of locoregional recurrence. Loss of p16 (67%) was associated with postoperative widespread metastases. Loss of Smad4 (60%) was associated with the tumor size and lymph node metastasis. Loss of Smad4 was an independent and significant poor prognostic factor for overall survival. On analysis of combinations of the status of these 3 genes, increasing number of alterations reflected poorer survival.
Genetic alterations of these 3 genes and their accumulation are strongly associated with malignant behavior of PDAC. Their assessment may provide a new prognostic tool, assisting in deciding optimal therapeutic strategies.