AIMS: Breast cancer 1 (BRCA1) expression is down-regulated in a significant proportion of non-hereditary breast cancers, in the absence of any mutation. This phenomenon is more pronounced in oestrogen (ER)-negative tumours. Recent studies have suggested that inhibitor of DNA binding 4 (ID4), as well as p53, participate in the transcriptional regulation of BRCA1. METHODS: Immunohistochemical expression of ID4, BRCA1, BRCA2 and p53 in 699 women with triple-negative breast cancer was investigated using tissue microarrays. The prognostic role of these biomarkers was also evaluated. Survival outcomes were estimated with the Kaplan-Meier method and compared between groups with log-rank statistics. RESULTS: Loss of BRCA1 and BRCA2 expression and overexpression of ID4 and p53 was observed in 75%, 90%, 95% and 66% of tumours, respectively. ID4 expression was increased in higher tumour grade (P < 0.001) and was associated significantly with basal-like subtype (P < 0.001), BRCA2 down-regulation (P = 0.037) and p53 accumulation (P < 0.001). Patients with strong ID4 expression displayed worse disease-free survival in both triple-negative breast cancers (P = 0.041) and basal-like triple-negative breast cancers (P = 0.026). CONCLUSION: There is frequent ID4 expression and concomitant loss of BRCA proteins in triple-negative breast cancer. We hypothesize that strong ID4 expression could be useful as a prognostic marker in triple-negative breast cancer, predicting early tumour recurrence.
AIMS: Breast cancer 1 (BRCA1) expression is down-regulated in a significant proportion of non-hereditary breast cancers, in the absence of any mutation. This phenomenon is more pronounced in oestrogen (ER)-negative tumours. Recent studies have suggested that inhibitor of DNA binding 4 (ID4), as well as p53, participate in the transcriptional regulation of BRCA1. METHODS: Immunohistochemical expression of ID4, BRCA1, BRCA2 and p53 in 699 women with triple-negative breast cancer was investigated using tissue microarrays. The prognostic role of these biomarkers was also evaluated. Survival outcomes were estimated with the Kaplan-Meier method and compared between groups with log-rank statistics. RESULTS: Loss of BRCA1 and BRCA2 expression and overexpression of ID4 and p53 was observed in 75%, 90%, 95% and 66% of tumours, respectively. ID4 expression was increased in higher tumour grade (P < 0.001) and was associated significantly with basal-like subtype (P < 0.001), BRCA2 down-regulation (P = 0.037) and p53 accumulation (P < 0.001). Patients with strong ID4 expression displayed worse disease-free survival in both triple-negative breast cancers (P = 0.041) and basal-like triple-negative breast cancers (P = 0.026). CONCLUSION: There is frequent ID4 expression and concomitant loss of BRCA proteins in triple-negative breast cancer. We hypothesize that strong ID4 expression could be useful as a prognostic marker in triple-negative breast cancer, predicting early tumour recurrence.
Authors: Magdalena Pruszko; Elisa Milano; Mattia Forcato; Sara Donzelli; Federica Ganci; Silvia Di Agostino; Simone De Panfilis; Francesco Fazi; David O Bates; Silvio Bicciato; Maciej Zylicz; Alicja Zylicz; Giovanni Blandino; Giulia Fontemaggi Journal: EMBO Rep Date: 2017-06-26 Impact factor: 8.807
Authors: Sara Donzelli; Elisa Milano; Magdalena Pruszko; Andrea Sacconi; Silvia Masciarelli; Ilaria Iosue; Elisa Melucci; Enzo Gallo; Irene Terrenato; Marcella Mottolese; Maciej Zylicz; Alicja Zylicz; Francesco Fazi; Giovanni Blandino; Giulia Fontemaggi Journal: Breast Cancer Res Date: 2018-06-19 Impact factor: 6.466