Journal of Clinical & Experimental Pathology
Open Access

Abstract

Molecular mechanisms of DNA damage and repair and factors interfering with it have been subject of numerous studies in the last decades. BRCA1 and BRCA2 associated breast and ovarian cancer have already been well established as a proof-of- concept for synthetic lethality by Poly(ADP-ribose) polymerase (PARP) inhibition that refers to the inability of BRCA-deficient cells to repair double strand breaks that emerge from single strand breaks in case of PARP inhibition of base excision repair. The aim of our study was to investigate immunohistochemical expression of PARP in breast cancers from patients with deleterious mutations in the BRCA1- (n = 67) or BRCA2-mutated (n = 29) gene compared to a cohort of sporadic breast cancers (n = 54). An immunostaining score ranging from 0 to 12 was calculated for nuclear PARP (nPARP). In parallel, stained slides were digitalized and evaluated independently by automated image analysis. nPARP staining patterns were significantly increased in both BRCA1- (p < .0001) and BRCA2-associated cancers (p < .0001). No significant expression levels in the sporadic forms were observed. nPARP levels were significantly increased in HR-positive BRCA-associated cancers compared to HR-positive sporadic cancers (p < 0.0001). No significant increase in nPARP expression in the few cases of sporadic triple-negative cancers was noticed. Our results suggest that nPARP expression is associated with BRCA dependent DNA repair deficiency. Further studies with larger cohorts are required to confirm this and its potential role as a predictive biomarker for PARP inhibition in hereditary as well as in sporadic breast cancer.

Biography

Luka Ozretic was born in Split, Croatia, in 1984. He gained his MD degree from the University of Zagreb School of Medicine in 2008 and is currently an anatomic pathology resident working in the University Hospital of Cologne, Germany. His fields of interest include breast pathology, cytopathology and hematopathology.