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The immunohistochemical expression of DNA-PKCS and Ku (p70/p80) in head and neck cancers: relationships with
T Björk-Eriksson1, C West, A Nilsson
1Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden. thomas.bjork-eriksson@oncology.gu.se
Purpose:
The DNA-PK complex is one of the major pathways by which mammalian cells respond to DNA double-strand breaks induced by ionizing radiation. This study evaluated the relationship between the immunohistochemical expression of the individual components of DNA-PK and cellular radiosensitivity in head and neck cancers.
Methods And Materials:
Biopsies from patients with previously untreated squamous cell carcinomas of the head and neck were assessed for inherent tumor radiosensitivity measured as the surviving fraction at 2 Gy (SF2) using a soft agar clonogenic assay. Paraffin-embedded tumor material from 64 successfully grown specimens was immunohistochemically stained for expression of DNA-PKcs and Ku (p70/p80). The same tumor material was previously analyzed for the immunohistochemical expression of p53.
Results:
A significant correlation was found between the degree of expression of DNA-PKcs and Ku (p70/p80) (r = 0.55, p<0.001). There were no overall significant differences in the levels of expression of DNA-PKcs and Ku (p70/p80) in tumors from patients of either sex, different sites, histologies, and stages. No relationship was found between SF2 and the expression of either DNA-PKcs (r = 0.22, p = 0.081) or Ku (p70/p80) (r = 0.064, p = 0.62). Comparison with previous immunohistochemical characterization showed no significant correlations between the expression levels of p53 and either DNA-PKcs (r = 0.093, p = 0.46) or Ku (p70/p80) (r = -0.17, p = 0.17).
Conclusions:
This study suggests that determining the immunohistochemical expression of DNA-PK in head and neck cancers from multiple sites does not have a role as a predictive assay of tumor in vitro radiosensitivity.
Insights
Assessing DNA-PK complex expression in head and neck cancers did not predict tumor radiosensitivity. Immunohistochemical analysis of DNA-PKcs and Ku showed no correlation with cellular radiosensitivity (SF2) in squamous cell carcinomas.
Area of Science:
- Oncology
- Molecular Biology
- Radiation Oncology
Background:
- The DNA-PK complex is crucial for repairing DNA double-strand breaks caused by ionizing radiation.
- Understanding DNA-PK's role is vital for predicting cancer treatment response.
- Head and neck cancers exhibit varied responses to radiotherapy.
Purpose of the Study:
- To investigate the association between immunohistochemical expression of DNA-PK components (DNA-PKcs and Ku) and cellular radiosensitivity in head and neck squamous cell carcinomas.
- To determine if DNA-PK expression can serve as a predictive biomarker for radiotherapy response.
Main Methods:
- Assessed inherent tumor radiosensitivity using the surviving fraction at 2 Gy (SF2) via soft agar clonogenic assay.
- Performed immunohistochemical staining for DNA-PKcs and Ku (p70/p80) on 64 head and neck cancer biopsy specimens.
- Correlated protein expression levels with SF2 values and previously analyzed p53 expression.
Main Results:
- A significant correlation was observed between DNA-PKcs and Ku expression levels (r = 0.55, p<0.001).
- No significant relationship was found between SF2 and the expression of DNA-PKcs (r = 0.22, p = 0.081) or Ku (r = 0.064, p = 0.62).
- No significant correlations were found between p53 expression and DNA-PKcs or Ku expression.
Conclusions:
- Immunohistochemical assessment of DNA-PK complex components (DNA-PKcs and Ku) in head and neck cancers does not serve as a predictive assay for in vitro tumor radiosensitivity.
- Current findings suggest that DNA-PK expression levels are not reliable indicators of radiosensitivity in this cancer type.