Early DNA damage response in residual carcinoma in situ at ductal stumps and local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma

  • Wakai Toshifumi
    Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences
  • Shirai Yoshio
    Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences
  • Sakata Jun
    Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences
  • Korita Pavel V.
    Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences
  • Ajioka Yoichi
    Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences
  • Hatakeyama Katsuyoshi
    Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences

Bibliographic Information

Other Title
  • 胆管癌根治切除後の胆管切離断端に遺残した上皮内癌における早期DNA損傷修復応答と局所再発との関連

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Abstract

To clarify the association between DNA damage response in tumor specimens of ductal resection margins and local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma. A retrospective analysis was conducted of 11 patients with positive ductal margins with carcinoma in situ. To evaluate the early DNA damage response, the nuclear staining pattern of p53-binding protein 1 (53BP1) was examined by immunofluorescence. Of the 11 tumor specimens of carcinoma in situ, 10 showed diffuse localization of 53BP1 in nuclei (53BP1 inactivation) and 4 showed discrete nuclear foci of 53BP1 (53BP1 activation); the apoptotic index was significantly decreased in the 7 tumor specimens with 53BP1 inactivation compared to the 4 with 53BP1 activation (median apoptotic index, 1% vs. 22%; p=0.003). Cumulative probability of local recurrence was significantly higher in patients with 53BP1 inactivation than in patients with 53BP1 activation (cumulative 5-year local recurrence rate, 60% vs. 0%; p=0.019). These data suggest that local recurrence is associated with 53BP1 inactivation and decreased apoptosis.<br>

Journal

  • Tando

    Tando 24 (5), 667-674, 2010

    Japan Biliary Association

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