Spatial relationship of phosphorylated epidermal growth factor receptor and activated AKT in head and neck squamous cell carcinoma.

ABSTRACT

BACKGROUND: Overexpression of EGFR correlates with decreased survival after radiotherapy in head and neck squamous cell carcinoma (HNSCC). However, the contribution of the activated form, pEGFR, and its downstream signaling (PI3-K/AKT) pathway is not clear yet. METHODS: Fifty-eight patients with HNSCC were included in the study. pEGFR, pAKT, hypoxia, and vessels were visualized using immunohistochemistry. Fractions (defined as the tumor area positive for the respective markers relative to the total tumor area) were calculated by automated image analysis and related to clinical outcome. RESULTS: Both pEGFR (median 0.6%, range 0-34%) and pAKT (median 1.8%, range 0-16%) expression differed between tumors. Also, a large variation in hypoxia was found (median pimonidazole fraction 3.9% 0-20%). A significant correlation between pEGFR and pAKT (r(s) 0.44, p=0.004) was seen, however, analysis revealed that this was not always based on spatial coexpression. Low pAKT expression was associated with increased risk of regional recurrence (p<0.05, log-rank) and distant metastasis (p=0.04). CONCLUSION: The correlation between expression of pEGFR and pAKT is indicative of activation of the PI3-K/AKT pathway through phosphorylation of EGFR. Since not all tumors show coexpression to the same extent, other factors must be involved in the activation of this pathway as well.