Troy Jesse D, Weissfeld Joel L, Youk Ada O, Thomas Sufi, Wang Lin, Grandis Jennifer R
Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, A516 Crabtree Hall, 130 DeSoto Street, Pittsburgh, PA, 15261, USA,
Head Neck Pathol. 2013 Dec;7(4):344-55. doi: 10.1007/s12105-013-0447-y. Epub 2013 May 4.
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 × percent of cells staining) by HPV status and lifestyle factors. Associations between EGFR, VEGF, and NOTCH1 were assessed using box plots and Spearman correlation (ρ) 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 (ρ = 0.40, P = 0.01) but not HPV-positive HNSCC (ρ = 0.25, P = 0.20). NOTCH1 and VEGF were associated in HPV-negative (ρ = 0.40, P = 0.01) but not HPV-positive tumors (ρ = -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.
目前对头颈部鳞状细胞癌（HNSCC）的抗血管生成疗法存在兴趣，尽管这些疗法在人乳头瘤病毒（HPV）阳性和HPV阴性的HNSCC中的效用尚不清楚。因此，我们在一个HNSCC病例系列中，通过免疫组织化学方法（N = 67例，通过原位杂交确定27例HPV阳性，40例HPV阴性），探究了血管生成中的一个远端因子（EGFR，表皮生长因子受体）、一个近端因子（VEGF，血管内皮生长因子）和一个假定因子（NOTCH1）的表达异质性。使用箱线图以及Wilcoxon秩和检验或Kruskal-Wallis检验，按HPV状态和生活方式因素比较染色分数（强度×染色细胞百分比）。在所有病例中，使用箱线图和Spearman相关性（ρ）评估EGFR、VEGF和NOTCH1之间的关联，并按HPV状态分层。相对于HPV阳性的HNSCC [7.5（0 - 200）]，HPV阴性的HNSCC过度表达EGFR [中位数（范围）：30（0 - 300）]（P = 0.006）。VEGF和NOTCH1与HPV状态无关（P > 0.05）。在HPV阴性的HNSCC中EGFR与VEGF相关（ρ = 0.40，P = 0.01），但在HPV阳性的HNSCC中不相关（ρ = 0.25，P = 0.20）。在HPV阴性的肿瘤中NOTCH1与VEGF相关（ρ = 0.40，P = 0.01），但在HPV阳性的肿瘤中不相关（ρ = -0.12，P = 0.57）。NOTCH1与EGFR不相关（P > 0.05）。我们的结果提示HNSCC血管生成存在异质性。未来的研究应探索HPV阳性和HPV阴性HNSCC中的血管生成机制。
