Osteonectin/SPARC Expression in Head and Neck Squamous Cell Carcinoma: A Tissue Microarray Study

Abstract

Some studies have correlated secreted protein acidic and rich in cysteine (SPARC) expression with more aggressive behavior in head and neck squamous cell carcinoma (SCC). We investigated the impact of SPARC expression on patient outcomes in a large cohort of SCCs. Patients with SCC were identified by searching institutional databases. A tissue microarray of paraffin-embedded tumor specimens was constructed, and SPARC immunohistochemistry was performed. Cellular and stromal SPARC expression were quantitated and correlated with clinicopathologic features. Of 191 cases, 171 were adequate for SPARC evaluation. A total of 112 (65%) cases showed SPARC tumor cell staining, and 167 (98%) cases showed stromal staining. Increased SPARC stromal expression was correlated with poorer overall survival (OS) [mean (SD) survival, 64.3 (3.25) vs. 42.8 (3.25) mo; P=0.0015] and poorer disease-specific survival (DSS) [mean (SD) survival, 51.1 (1.58) vs. 38.3 (1.832) mo; P=0.0381]. Human papillomavirus-positive status correlated with both stromal and tumor SPARC expression (P=0.0047 and 0.0408, respectively). SPARC staining did not correlate with OS or DSS in multivariate analyses. Among nonchemotherapy patients, SPARC stromal expression was associated with poorer OS and DSS (P=0.0074 and 0.033, respectively). In multivariate analyses, increased stromal SPARC expression was associated with a longer disease-free interval [P=0.0170 (hazard ratio, 1.384)]. SPARC expression is frequently present in tumoral stroma of head and neck SCCs. In contravention to prior studies, we found that SPARC expression did not correlate with survival overall. This suggests that previously reported associations may not, in fact, exist highlighting the need to meticulously adjust for confounding variables in novel biomarker studies. However, subgroup analysis showed that stromal SPARC expression is associated with better disease-free survival among patients who are not treated with chemotherapy.