Analysis of Osteopontin Expression in HER2-Positive and Basal/Triple Negative Breast Carcinomas
E Alcaraz, M Planelles, D Giner, L Sanchez-Tejada, T Muci, FI Aranda, G Peiro. Hospital General Universitari, Alacant, Spain
Background: Osteopontin (OPN) is a multifunctional protein found in a variety of normal and neoplastic tissues. A few recent studies in breast carcinoma (BC) have suggested an association with adverse pathological and poorer clinical outcome. The aim of our study was to evaluate OPN expression in a series of BC with an aggressive phenotype, such as HER2-positive and basal/triple-negative (TN) to determine its prognostic value.
Design: OPN expression was studied immunohistochemically (IHC) on paraffin-embedded tissue micro-arrays of 234 BC: 142 (60.7%) HER2-positive (3+ in >30% cells by IHC or amplification by FISH/CISH), and 92 (39.3%) basal/TN (ER/PR/HER2-negative +/- CK5/6 +/- EGFR). OPN cytoplasm staining was semiquantitatively scored based on intensity (0-3+) and distribution (0-100%) (score 0-300). The results were correlated with clinico-pathological variables and patients' outcome. Data was statistically analyzed using Chi-square or Fisher's exact tests, and survival was calculated by the Kaplan-Meier method (log-rank test).
Results: Median patients' age was 56 years (range 28-87 years) with a median follow-up of 65 months. In this series, tumors were more frequently >20 mm (54%) in size, of grade 3 (72%), and lymph-node status negative (56%). OPN overexpression (score >50) was observed in 33.5% BC. Among them, were found those presenting in older patients (84%; p=0.019), of high grade (83%; p=0.044), with positive lymph-node status (65%; p=0.042) and basal/TN immunophenotype (76%; p<0.000). However, no correlation was observed for tumor size, the presence of necrosis or vascular invasion (p=ns). Survival analyses stratified by immunophenotypes demonstrated that HER2/OPN-positive patients compared with those with HER2/OPN-negative, had a trend towards poorer disease-free (25% vs 61%; p=0.11) and overall survival (40% vs 73%; p=0.058), but no differences were seen for the basal/TN/OPN-positive group (p=ns).
Conclusions: In the current series of BC, OPN overexpression was related with unfavorable prognostic factors, and a negative impact on survival in patients with HER2-positive tumors. Thus, our results support that OPN is a potential marker of poor prognosis and it may represent an attractive target of therapy.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 49, Tuesday Morning