Dissected peripancreatic tissue margin is a critical prognostic factor and is associated with a K-ras gene mutation in pancreatic ductal adenocarcinoma

Nobuyuki Nishizawa; Yusuke Kumamoto; Hiroshi Katoh; Hideki Ushiku; Keigo Yokoi; Toshimichi Tanaka; Satoru Ishii; Kazuharu Igarashi; Hiroshi Tajima; Takashi Kaizu; Tsutomu Yoshida; Makoto Saegusa; Masahiko Watanabe; Keishi Yamashita

doi:10.3892/ol.2018.9839

Dissected peripancreatic tissue margin is a critical prognostic factor and is associated with a K-ras gene mutation in pancreatic ductal adenocarcinoma

Oncol Lett. 2019 Feb;17(2):2141-2150. doi: 10.3892/ol.2018.9839. Epub 2018 Dec 17.

Authors

Affiliations

¹ Department of Surgery, Kitasato University Hospital, Sagamihara, Kanagawa 252-0374, Japan.
² Department of Pathology, Kitasato University Hospital, Sagamihara, Kanagawa 252-0374, Japan.
³ Division of Advanced Surgical Oncology, Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan.

Abstract

We previously reported that the dissected pancreatic tissue margin (DPM) and the preoperative serum level of carbohydrate antigen 19-9 (preCA19-9) were independent prognostic factors in pancreatic ductal adenocarcinoma (PDAC). In the current study, the prognostic relevance of these factors, including their molecular associations, were validated. A total of 161 patients with PDAC underwent a pancreatectomy between 1986 and 2013, and a multivariate Cox proportional hazards model and a propensity score-based model validated the prognostic importance of DPM. The prognostic factors were compared with the mutation profiles of the K-ras and TP53 genes. Univariate prognostic analysis of disease-specific survival (DSS) demonstrated that DPM (P<0.0001), preCA19-9 (P<0.0001) and Union for International Cancer Control (UICC) stage (P<0.0001), were all significantly associated with poor outcome in PDAC. A multivariate Cox proportional hazards model confirmed that preCA19-9 (P=0.0002) and DPM (P=0.0002) remained as prognostic factors independent of UICC stage (P=0.0015). The combination of preCA19-9 and DPM to predict prognosis could accurately identify the long-term survivors of PDAC (70% 5-year DSS), and a multivariate logistic regression model identified that DPM was the most effective predictor of mortality. The prognostic relevance of DPM was also confirmed (P=0.0008) through propensity score-based background adjustment of patient bias. K-ras gene mutation was significantly associated with DPM (P=0.0002), and DPM-positive patients demonstrated recurrence of distant metastasis in 67% of cases. Therefore, DPM is a critical prognostic indicator in PDAC. In combination with preCA19-9, DPM may be useful to identify long-term survivors of PDAC. Furthermore, to the best of our knowledge, the current study was the first to discover that DPM can represent a poor prognosis based putatively on its association with the K-ras gene mutation.

Keywords: K-ras; carbohydrate antigen 19-9; dissected peripancreatic tissue margin; prognostic factor.