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

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

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

Authors:
- 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
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Affiliations: Department of Surgery, Kitasato University Hospital, Sagamihara, Kanagawa 252‑0374, Japan, Department of Pathology, Kitasato University Hospital, Sagamihara, Kanagawa 252‑0374, Japan
Published online on: December 17, 2018 https://doi.org/10.3892/ol.2018.9839
Pages: 2141-2150
Copyright: © Nishizawa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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