A52: Detection and analysis of ?H2AX expression by immunohistochemistry as a marker of in situ breast cancer

Ramon Boghozian1,Christiana Kartsonaki3,1,Ioannis Roxanis4,Russell Leek5,Adrian Harris2,Katherine Vallis1

1Department of Radiation Oncology, CRUK/MRC Oxford Institute for Radiation Oncology, Oxford University, Oxford, UK,2Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK,3Bioinformatics Group, University of Oxford, Old Road Campus Research Building, Oxford, UK,4Department of Cellular Pathology, Oxford University Hospitals and NIHR Biomedical Research Centre Oxford, Oxford, UK,5Nuffield Division of Clinical Laboratory Science, Radcliffe Department of Medicine, University of Oxford, Oxford, UK

Presenting date: Monday 2 November
Presenting time: 13.10-14.00

Background

Breast cancer is the most common cancer in females worldwide. Ductal carcinoma in situ (DCIS) represents an early, non-invasive form of breast cancer. Oncogenic driven proliferation causes activation of the DNA damage response, which has been associated with pre-neoplastic lesions in a number of tissues. This opens the possibility of employing DNA damage biomarkers for early detection of breast cancer. A histone variant termed ?H2AX is readily detectable at sites of DNA damage during oncogenic transformation. Therefore, the aim of the project was to examine the expression of ?H2AX in early breast neoplasia and to elucidate its role as a candidate biomarker in association with various clinical parameters.

 

 

Method

Formalin-fixed, paraffin-embedded (FFPE) human tissue microarrays, consisting of 120 DCIS and 182 invasive breast carcinomas (IBCs) were used for this study. Chromogenic immunohistochemistry (IHC) was performed to examine the expression of ?H2AX. This was measured using a semi-quantitative method, involving an automated software program (Immunoratio®) and two independent scoring observers. Manual scoring was performed using a scaled system assessing the proportion of ?H2AX-positive cells and staining intensity

Results

There was higher average cell-positive proportion of ?H2AX in DCIS compared to IBC (32.2% vs 5.58%, p<0.001). Higher ?H2AX expression was also associated with decreased risk of relapse in DCIS patients only (HR 0.57, p=0.03).

Conclusion

The results indicate that ?H2AX has potential as a biomarker of early breast neoplasia, specifically DCIS. Further characterization of associated DDR proteins is needed to determine the potential value of ?H2AX as a clinical biomarker.