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Influence of Ku86 and XRCC4 expression in uterine cervical cancer on the response to preoperative radiotherapy

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Abstract

DNA double-strand breaks (DSB) are severe damages induced by ionizing radiation. Non-homologous end joining (NHEJ) is a major mechanism for repairing DSB. Immunohistochemical analysis of proteins involved in NHEJ, such as Ku86 and XRCC4 (X-ray repair cross-complementing protein 4) may be useful for predicting tumor radiosensitivity. We examined the relationship between expression of DSB-related proteins in biopsy specimens of uterine cervical cancer and the pathological effect of 40 Gy of preoperative radiotherapy. 119 patients with uterine cervical cancer were treated between 2000 and 2011. Pathological effects of preoperative radiotherapy were classified by examining hysterectomy specimens. Patients with complete response (pCR) had a significantly better overall 5-year survival rate than those without pCR (96.3 vs. 76.9 %, P = 0.02). The pCR rate was significantly higher in patients with low Ku86 and XRCC4 expression than in other patients (47.4 vs. 21.3 %, P = 0.04). Logistic regression analysis also demonstrated that low Ku86 and XRCC4 expression was a significant predictor of pCR (P = 0.03). Patients with high Ku86 and XRCC4 expression had a significantly lower 5-year metastasis-free rate than others (79.3 vs. 93.5 %, P = 0.02). Proteins involved with NHEJ might have an influence on results of radiotherapy for uterine cervical cancer.

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Acknowledgments

The research were supported in part by a Grant-in Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan. I would like to thank Dr. Masanori Nojima (The insituite of Medical Science Hospital, The University of Tokyo) for useful advices about statistical analysis.

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Authors and Affiliations

  1. Department of Radiology, School of Medicine, Sapporo Medical University, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan

    Yu Takada, Masanori Someya, Kensei Nakata, Masakazu Hori, Masato Saito, Naoki Hirokawa, Kunihiko Tateoka & Koh-ichi Sakata

  2. Tokyo Institute of Technology, Research Laboratory for Nuclear Reactors, Tokyo, Japan

    Yoshihisa Matsumoto

  3. Division of Clinical Pathology, NTT Sapporo Hospital, Sapporo, Hokkaido, Japan

    Masaaki Satoh

  4. Department of Obstetrics and Gynecology, School of Medicine, Sapporo Medical University, Sapporo, Hokkaido, Japan

    Mizue Teramoto & Tsuyoshi Saito

  5. Department of Surgical Pathology, School of Medicine, Sapporo Medical University, Sapporo, Hokkaido, Japan

    Tadashi Hasegawa

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  1. Yu Takada
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  2. Masanori Someya
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  3. Yoshihisa Matsumoto
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  4. Masaaki Satoh
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  5. Kensei Nakata
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  6. Masakazu Hori
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  7. Masato Saito
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  8. Naoki Hirokawa
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  9. Kunihiko Tateoka
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  10. Mizue Teramoto
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  11. Tsuyoshi Saito
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  12. Tadashi Hasegawa
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  13. Koh-ichi Sakata
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Correspondence to Koh-ichi Sakata.

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Takada, Y., Someya, M., Matsumoto, Y. et al. Influence of Ku86 and XRCC4 expression in uterine cervical cancer on the response to preoperative radiotherapy. Med Mol Morphol 49, 210–216 (2016). https://doi.org/10.1007/s00795-016-0136-5

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  • DOI: https://doi.org/10.1007/s00795-016-0136-5

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