Abstract
5548 Background: We studied associations between recurrence-free survival (RFS) and expression levels of hypoxia-inducible factor-1 alpha (HIF-1a) and its activated (phosphorylated) upstream molecules mammalian target of rapamycin (mTOR), epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) in SCCOT of patients treated homogeneously with surgery ± radiotherapy. Methods: TMAs of 113 resected SCCOT were immunohistochemically stained with antibodies against pEGFR, pIGF-1R, p mTOR and HIF-1a. Scoring equaled intensity of staining (0–3) in each cellular compartment (membrane, cytoplasm and nucleus) times the percentage of stained cells (0%–100%). Marker associations were analyzed via the Spearmen correlation coefficient (SC). Impact of clinical variables or biomarkers on RFS was assessed in the Cox proportional hazards model. Results: Univariate analysis showed that T and N stage, depth of muscle invasion, extracapsular lymph node spread, and perineural invasion were associated with decreased RFS (p<0.05). There was no correlation between pEGFR and p mTOR, pIGF-1R and p mTOR, pEGFR and HIF-1a, pIGF-1R and HIF-1a, or p mTOR and HIF-1a (p>0.05). We found a statistically significant correlation between membrane pEGFR and cytoplasmic pIGF-1R (SC=0.24, p=0.04). There were no statistically significant associations between any marker and RFS (p>0.05). Conclusions: We found no association between HIF-1a and upstream, phosphorylated EGFR, IGF-1R, or mTOR. The positive correlation between pEGFR and pIGF-1R may signify cross-phosphorylation between these receptors, as previously found in other tumor types in vitro. No marker correlated with RFS. Although needing validation in prospectively collected specimens for phospho-protein studies, our preliminary data suggest that multiple pathways (rather than any single marker alone) activate key signaling molecules leading to recurrence. Thus, we continue to assess additional markers in the TMAs to characterize the potentially relevant pathways more comprehensively. Supported by The ASCO Cancer Foundation (YIA)/Head and Neck SPORE P50CA097007. No significant financial relationships to disclose.
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