Immunohistochemically Detected Expression of Three Major Genes (CDKN2A/p16,TP53 and SMAD4/DPC4) Strongly Predicts Survival in Patients with Pancreatic Cancer

2014 Fiscal Year Final Research Report

• Project/Area Number: 24592029
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kagawa University
• Principal Investigator: OSHIMA Minoru 香川大学, 医学部附属病院, 助教 (60624830)
• Co-Investigator(Kenkyū-buntansha): YACHIDA Shinichi 独立行政法人国立がん研究センター, 研究所がんゲノミクス研究分野, ユニット長 (20359920) ; OKANO Keiichi 香川大学, 消化器外科, 准教授 (20314916) ; SUZUKI Yasuyuki 香川大学, 消化器外科, 教授 (40304092)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 通常型膵管癌 / 遺伝子異常

Outline of Final Research Achievements

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.

Free Research Field

消化器外科