The aim of this study was to examine the loss of heterozygosity (LOH) of BRCA1 (17q21) and TP53 (17p13.1) in early-onset breast cancer patients; to correlate biopathological characteristics with molecular alterations; and to investigate the survival of LOH-related cancers. BRCA1 and TP53 LOH were evaluated in 78 early-onset breast cancers (< or = 40 years, Group 1) and 80 patients with age > 55 years (Group 2). Cases were characterized for multiple biological markers (ER, PR, proliferation index (PI), NEU and p53). LOH was carried out on microdissected paraffin embedded tissues; microsatellites D17S855 (BRCA1) and D17S786 (TP53) were amplified by fluorescent PCR and analyzed by an automated DNA sequencer. Early-onset breast cancers showed a higher frequency of ductal histotype (89.7% vs. 56.3% p < 0.001), node-positive (53.8% vs. 38.7%), larger size (p = 0.017), higher mitotic rate (p = 0.025), higher nuclear and final grade (p = 0.01 and p = 0.001, respectively). D17S855 LOH was 32.8% in group 1 vs. 21% in group 2; D17S786 LOH was 50.7% vs. 31.3% (p = 0.03), respectively. BRCA1 LOH was correlated with higher PI (p = 0.032) and higher p53 expression (p < 0.001) in group 1 and with higher NEU expression (p = 0.028) in group 2. TP53 LOH was correlated with p53 overexpression (p = 0.03) in group 1. A worse clinical outcome in early-onset LOH related cancers emerged from follow-up data: TP53 and BRCA1 LOH were associated with a shorter relapse free interval (RFI) (p = 0.03) and a poorer overall survival (OS) (p = 0.04), respectively. This study underlines different biological profiles in the two age groups investigated, probably reflecting different mechanisms of carcinogenesis. In accordance with adverse histopathological features in early-onset patients, LOH-related cancers have an unfavorable prognosis.
Biophenotypes and survival of BRCA1 and TP53 deleted breast cancer in young women
QUERZOLI, Patrizia;DI IASIO, Maria Grazia;FERRETTI, Stefano;PEDRIALI, Massimo;MATTEUZZI, Maurizio;MAESTRI, Iva;NENCI, Italo
2001
Abstract
The aim of this study was to examine the loss of heterozygosity (LOH) of BRCA1 (17q21) and TP53 (17p13.1) in early-onset breast cancer patients; to correlate biopathological characteristics with molecular alterations; and to investigate the survival of LOH-related cancers. BRCA1 and TP53 LOH were evaluated in 78 early-onset breast cancers (< or = 40 years, Group 1) and 80 patients with age > 55 years (Group 2). Cases were characterized for multiple biological markers (ER, PR, proliferation index (PI), NEU and p53). LOH was carried out on microdissected paraffin embedded tissues; microsatellites D17S855 (BRCA1) and D17S786 (TP53) were amplified by fluorescent PCR and analyzed by an automated DNA sequencer. Early-onset breast cancers showed a higher frequency of ductal histotype (89.7% vs. 56.3% p < 0.001), node-positive (53.8% vs. 38.7%), larger size (p = 0.017), higher mitotic rate (p = 0.025), higher nuclear and final grade (p = 0.01 and p = 0.001, respectively). D17S855 LOH was 32.8% in group 1 vs. 21% in group 2; D17S786 LOH was 50.7% vs. 31.3% (p = 0.03), respectively. BRCA1 LOH was correlated with higher PI (p = 0.032) and higher p53 expression (p < 0.001) in group 1 and with higher NEU expression (p = 0.028) in group 2. TP53 LOH was correlated with p53 overexpression (p = 0.03) in group 1. A worse clinical outcome in early-onset LOH related cancers emerged from follow-up data: TP53 and BRCA1 LOH were associated with a shorter relapse free interval (RFI) (p = 0.03) and a poorer overall survival (OS) (p = 0.04), respectively. This study underlines different biological profiles in the two age groups investigated, probably reflecting different mechanisms of carcinogenesis. In accordance with adverse histopathological features in early-onset patients, LOH-related cancers have an unfavorable prognosis.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
