Journal
HEAD & NECK PATHOLOGY
Volume 7, Issue 4, Pages 344-355Publisher
SPRINGER
DOI: 10.1007/s12105-013-0447-y
Keywords
Head and neck neoplasms; Receptor, epidermal growth factor; Receptor, NOTCH1; Vascular endothelial growth factors; Angiogenic proteins
Categories
Funding
- Tissue and Research Pathology Services Laboratory at University of Pittsburgh Medical Center
- National Institutes of Health [P50 CA097190, R25 CA057703]
- American Cancer Society
- Department of Epidemiology within Graduate School of Public Health at University of Pittsburgh
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There is current interest in anti-angiogenesis therapies for head and neck squamous cell carcinomas (HNSCC), although the utility of these therapies in human papillomavirus (HPV) positive and HPV-negative HNSCC is unclear. Therefore, we explored heterogeneity in expression of a distal factor in angiogenesis (EGFR, the epidermal growth factor receptor), a proximal factor in angiogenesis (VEGF, the vascular endothelial growth factor) and a putative factor in angiogenesis (NOTCH1) in a HNSCC case series using immunohistochemistry in N = 67 cases (27 HPV-positive, 40 HPV-negative, by in situ hybridization). Box plots and the Wilcoxon rank sum or Kruskal-Wallis tests were used to compare staining scores (intensity 9 percent of cells staining) by HPV status and lifestyle factors. Associations between EGFR, VEGF, and NOTCH1 were assessed using box plots and Spearman correlation (rho) in all cases, and stratified by HPV status. HPV-negative HNSCC over-expressed EGFR [median (range): 30 (0-300)] relative to HPV-positive HNSCC [7.5 (0-200)] (P = 0.006). VEGF and NOTCH1 were unrelated to HPV status (P > 0.05). EGFR was associated with VEGF in HPV-negative (rho = 0.40, P = 0.01) but not HPV-positive HNSCC (rho = 0.25, P = 0.20). NOTCH1 and VEGF were associated in HPV-negative (rho = 0.40, P = 0.01) but not HPV-positive tumors (rho = -0.12, P = 0.57). NOTCH1 was not associated with EGFR (P > 0.05). Our results are suggestive of heterogeneity in HNSCC angiogenesis. Future studies should explore angiogenesis mechanisms in HPV-positive and HPV-negative HNSCC.
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