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Expression of DNA damage response proteins and complete remission after radiotherapy of stage IB-IIA of cervical cancer.
Department of Gynaecologic Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden..
Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden.
Unit of Medical Radiation Biology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
Department of Oncology and Pathology, Karolinska University Hospital, Stockholm, Sweden..
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2006 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 94, no 11, 1683-1689 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2006. Vol. 94, no 11, 1683-1689 p.
Keyword [en]
cervical cancer; radiosensitivity; DNA-PK; p53; p21; Mdm2
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-133694DOI: 10.1038/sj.bjc.6603153ISI: 000237950700022PubMedID: 16685270Scopus ID: 2-s2.0-33745257582OAI: oai:DiVA.org:liu-133694DiVA: diva2:1062625
Available from: 2017-01-07 Created: 2017-01-07 Last updated: 2017-04-21Bibliographically approved

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CiteExportLink to record
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