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Expression of DNA damage response proteins and complete remission after radiotherapy of stage IB-IIA of cervical cancer.

Beskow, C (author)
Karolinska Institutet
Kanter, L (author)
Karolinska Institutet
Holgersson, A (author)
Unit of Medical Radiation Biology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
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Nilsson, B (author)
Department of Oncology and Pathology, Karolinska University Hospital, Stockholm, Sweden.
Frankendal, B (author)
Department of Gynaecologic Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden.
Åvall-Lundqvist, Elisabeth (author)
Department of Gynaecologic Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden.
Lewensohn, R (author)
Karolinska Institutet
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 (creator_code:org_t)
2006-05-09
2006
English.
In: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 94:11, s. 1683-1689
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • The primary aim of this study was to investigate if the expression of the DNA damage identifying protein DNA-PKcs known to be involved in DNA repair after treatment with ionising radiation can be used as a predictive marker for radiotherapy (RT) response in cervical cancer. Formalin-fixed primary tumour biopsies from 109 patients with cervical cancer, FIGO-stage IB-IIA, treated with preoperative brachytherapy followed by radical surgery were analysed by immunohistochemistry. In addition, correlation studies between early pathological tumour response to radiation and expression of Ku86, Ku70, Mdm-2, p53 and p21 in primary tumours were also performed. We found that tumour-transformed tissue shows positive immunostaining of DNA-PKcs, Ku86 and Ku70, while non-neoplastic squamous epithelium and tumour-free cervix glands show negative immunoreactivity. Expression of DNA-PKcs positively correlated with both Ku86 and Ku70, and a statistically significant correlation between the Ku subunits was also found. After RT, 85 patients demonstrated pathologic complete remission (pCR), whereas 24 patients had residual tumour in the surgical specimen (non-pCR). The main finding of our study is that there was no correlation between the outcome of RT and the expression of DNA-PK subunits. Positive p53 tumours were significantly more common among non-pCR cases than in patients with pCR (P=0.031). Expression of p21 and Mdm-2 did not correlate with the outcome of RT.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Keyword

cervical cancer; radiosensitivity; DNA-PK; p53; p21; Mdm2

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