Stromal Osteonectin/SPARC Expression Predicts Aggressive Behavior in a Subset of Head and Neck Squamous Cell Carcinomas
M Hussaini, J Zhang, J Lewis, Jr. Washington University, St. Louis, MO
Background: SPARC/osteonectin is a 43 kD matricellular protein involved in cell-matrix interactions, particularly in remodeling tissues such as tissues undergoing morphogenesis, mineralization, angiogenesis, or pathological responses to injury and tumorigenesis. It is normally expressed by osteoblasts and seems to have a counter-adhesive effect on cells by disrupting cell matrix interactions. Overexpression of SPARC is seen in various cancers including its recent observation in head and neck squamous cell carcinomas (SCC), with over-expression suggested to predict poorer survival.
Design: Paraffin-embedded tissue microarrays (TMAs) consisting of two tumor punches per case were constructed from 192 non-selected head and neck SCC. These were immunohistochemically stained for SPARC. TMA slides were digitally scanned and then manually graded. Composite tumor and stromal SPARC scores (0-8) were assigned based on quartile percentage and strength of staining in the tumor cells and intra/peritumoral stroma, respectively. Correlation of pathologic findings and survival time was examined by log rank tests based on histologic tumor subtype (typical keratinizing SCC or K-SCC vs. nonkeratinizing oropharyngeal SCC or NK-SCC).
Results: Of the total of 192 cases, 174 were evaluable for SPARC staining. 107 were K-SCC of numerous primary sites and 67 were NK-SCC of the oropharynx. Analysis of the entire group showed that SPARC expression did not correlate with overall or disease specific survival. In the K-SCC group, a SPARC stromal score of 7 or greater (p=0.038) but not tumor cell staining (p=0.428) correlated with differentiation (well, moderately, poorly); however, neither correlated with overall or disease specific survival. In the NK-SCC group, a SPARC stromal score of 7 or greater strongly correlated with both poorer overall (p= 0.0106) and disease specific survival (p = 0.0477). SPARC tumor cell staining did not correlate with outcome.
Conclusions: SPARC/osteonectin stromal staining is associated with poorer overall and disease specific survival in oropharyngeal non-keratinizing SCC. We do not confirm the results of a prior smaller study which suggested that SPARC expression predicts poorer survival in SCC of the head and neck from various sites combined, although our data does show a similar trend. Further investigation is necessary, but SPARC staining may nonetheless serve as a useful prognostic marker in the appropriate context.
Category: Head & Neck
Monday, March 9, 2009 1:00 PM
Poster Session II # 172, Monday Afternoon