Osteopontin and Osteopontin-c Protein and mRNA Expression Correlate with Breast Cancer Aggressiveness.
Gloria Peiro, Fernando Ortiz-Martinez, Enrique Lerma, Encarna Adrover, Maria Planelles, Laura Sanchez-Tejada, Francisco I Aranda, Francisco J Gutierrez-Avino, Daniel Giner. Hospital General Universitari d'Alacant, Spain; Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Background: Osteopontin (OPN) is a secreted non-collagenous phosphoprotein that functions as both an extracellular matrix (ECM) component and a cytokine. Experimental and clinical studies suggest its association with tumor development, invasion and metastasis. The aim of this study was to investigate OPN (total and splice variant -c) protein and mRNA expression in a series of breast carcinoma (BC).
Design: We studied OPN-t and OPN-c expression immunohistochemically (IHC) on paraffin-embedded tissue microarrays containing 440 BC, stratified by immunophenotypes: 25% Luminal A and B (ER/PR+), 43% HER2+ (≥30% cells 3+ by IHC and/or FISH/CISH amplification), and 32% basal/TN (ER/PR/HER2-negative +/-CK5/6+/-EGFR). Cytoplasm staining was semiquantitatively scored based on intensity (0-3+) and distribution (0-100%) (score 0-300). We further analyzed OPN-t and OPN-c mRNA expression by real-time quantitative PCR in 120 samples. The correlation between OPN results and clinicopathological factors was evaluated.
Results: Median patients' age was 55 years (range 28-89) with a median follow-up of 90 months. OPN-t overexpression (34%) was found more frequent among tumors of older patients (73%; p<0.000), grade 3 (71%; p=0.03), basal/TN subtype, (61%; <0.000) and vascular invasion (54%; p=0.10). OPN-c was detected in larger tumors (57%; p=0.03), grade 3 (66%; p=0.03), HER2 subtype (48%; p=0.001), with positive lymph-node status (58%; p=0.017) and vascular invasion (52%; p=0.07). Similarly, increased OPN-c mRNA was associated with larger tumors (64%; p=0.09), positive lymph nodes (83%; p=0.003) and advanced stage (III-IV) (54%; p=0.005).
Conclusions: Our results support that increased levels of OPN-t and especially the OPN-c splice variant are related with breast cancer aggressiveness. Therefore, OPN has a potential value as a tumor progression marker and a target for its functional suppression. Supported by Grants FCVI-HGUA (PI-C/2008/02), ACOMP/2009/195 and GE-018/09
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 25, Wednesday Afternoon