55P - Evaluation of the role of MCPH1 and p53 expression in response to chemotherapy and subsequent survival in breast cancer

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer
Translational Research
Presenter Aeshah Awaji
Citation Annals of Oncology (2015) 26 (suppl_3): 15-24. 10.1093/annonc/mdv117
Authors A.A. Awaji1, A. Shaaban2, S. Shukla1, J. Bond1, E. Morrison1, V. Cookson1, S. Bell1
  • 1Wellcome Trust Brenner Building, Level 8 (section Of Opthalmology & Neuroscience), Leeds Institute of Biomedical & Clinical Sciences (LIBACS), LS9 7TF - Leeds/UK
  • 2Pathology, Queen Elizabeth-University Hospital Birmingham NHS Foundation Trust, B15 2TH - Birmingham/UK

Abstract

Body

Purpose: MCPH1, a DNA repair protein, has been implicated in the regulation of p53 stability in breast cancer (BC) cell lines. MCPH1 deficiency correlates with poor prognosis and reduced chemosensitivity in BC. This study examined the expression of MCPH1 in BC tissue samples, pre and post chemotherapy, to determine its predictive value in response to chemotherapy or survival, for the first time. The correlation between MCPH1 and p53 expression was also investigated in these BC samples.

Methods: MCPH1 and p53 expression levels were evaluated by immunohistochemistry in 133 pre chemotherapy and 54 matched pairs of post chemotherapy BC tissue samples. The correlation between changes in expression and overall survival (OS) were evaluated by Pearson paired parametric t test and Kaplan-Meier analysis, respectively. The Chi-square test/Fisher exact test was used for comparison among categorical data.

Results: There was a significant increase in MCPH1 expression after chemotherapy treatment (p < 0.0001). In contrast, no significant change in p53 expression in response to chemotherapy was identified. Pre chemotherapy expression of MCPH1 was strongly correlated with longer OS in patients with low MCPH1 expression (p = 0.007) compared to patients with high MCPH1 levels. There was no significant difference between patients expressing high or low MCPH1 post chemotherapy and estimated OS. However, p53 negative BC patients had significantly better OS post chemotherapy compared to those with positive p53 (p = 0.009). A significant association between MCPH1 and p53 staining scores before chemotherapy (p = 0.013), but not after chemotherapy, was observed.

Conclusion: In pre chemotherapy BC samples high levels of MCPH1 could be a clinical predictor of a poor response to therapy and reduced survival. Similarly, induction of MCPH1 expression by chemotherapy in BC patients may result in development of drug resistance. P53 negative tumours predict better OS after chemotherapy compared to p53 positive tumours. The significant correlation between MCPH1 and p53 pre chemotherapy confirms the hypothesis that high MCPH1 expression stabilizes p53 function and may influence response to chemotherapy and survival.

Disclosure: All authors have declared no conflicts of interest.