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

Journal of Hepato-Biliary-Pancreatic Sciences

Abstract

Background/purpose

The aim of this study was to clarify the association between the DNA damage response mediated by p53-binding protein 1 (53BP1) in residual carcinoma in situ at ductal stumps and local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma.

Methods

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 53BP1 was examined by immunofluorescence. TUNEL analysis was used to calculate the apoptotic index.

Results

Of the 11 tumor specimens of carcinoma in situ, seven showed diffuse localization of 53BP1 in nuclei (53BP1 inactivation) and four showed discrete nuclear foci of 53BP1 (53BP1 activation); the apoptotic index was significantly decreased in the seven tumor specimens with 53BP1 inactivation compared to the four with 53BP1 activation (median apoptotic index, 1 vs. 22 %; p = 0.003). The 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).

Conclusions

Clinically evident local recurrence of residual carcinoma in situ at ductal stumps is closely associated with 53BP1 inactivation and decreased apoptosis.

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Acknowledgments

The authors would like to thank Professor Kouhei Akazawa, Department of Medical Informatics, Niigata University Medical and Dental Hospital, Niigata, Japan, for suggestions concerning interpretation of statistical analysis in the present manuscript.

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None.

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Correspondence to Toshifumi Wakai.

Additional information

This article is a secondary publication based on a study first reported in the JBA (Journal of Japan Biliary Association) 2010;24:667–674.

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Wakai, T., Shirai, Y., Sakata, J. et al. Early DNA damage response in residual carcinoma in situ at ductal stumps and local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma. J Hepatobiliary Pancreat Sci 20, 362–369 (2013). https://doi.org/10.1007/s00534-012-0539-1

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  • DOI: https://doi.org/10.1007/s00534-012-0539-1

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