Expression of EGFR, VEGF, and NOTCH1 Suggest Differences in Tumor Angiogenesis in HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma
Expression of EGFR, VEGF, and NOTCH1 Suggest Differences in Tumor Angiogenesis in HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma
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DOI：
10.1007/s12105-013-0447-y
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发表时间：
2013-12-01
影响因子：
2.1
通讯作者：
Grandis, Jennifer R.
中科院分区：
文献类型：
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作者：
Troy, Jesse D.;Weissfeld, Joel L.;Grandis, Jennifer R.
目前人们对头颈部鳞状细胞癌（HNSCC）的抗血管生成疗法很感兴趣，尽管这些疗法在人乳头瘤病毒（HPV）阳性和HPV阴性的HNSCC中的应用尚不清楚。因此，我们在67例HNSCC病例（27例hpv阳性，40例hpv阴性，原位杂交）中，利用免疫组织化学方法探讨了远端血管生成因子（EGFR，表皮生长因子受体）、近端血管生成因子（VEGF，血管内皮生长因子）和推定血管生成因子（NOTCH1）表达的异质性。箱形图和Wilcoxon秩和或Kruskal-Wallis试验用于比较HPV状态和生活方式因素的染色评分（细胞染色强度的9%）。在所有病例中，使用箱形图和Spearman相关性（rho）评估EGFR、VEGF和NOTCH1之间的关联，并根据HPV状态分层。hpv阴性HNSCC过表达EGFR[中位数（范围）：30(0-300)]相对于hpv阳性HNSCC [7.5 (0-200)] （P = 0.006）。VEGF、NOTCH1与HPV状态无关（P < 0.05）。hpv阴性HNSCC中EGFR与VEGF有相关性（rho = 0.40, P = 0.01）， hpv阳性HNSCC中EGFR与VEGF无相关性（rho = 0.25, P = 0.20）。NOTCH1与VEGF在hpv阴性肿瘤中有相关性（rho = 0.40, P = 0.01），而在hpv阳性肿瘤中无相关性（rho = -0.12, P = 0.57）。NOTCH1与EGFR无相关性（P < 0.05）。我们的结果提示HNSCC血管生成的异质性。未来的研究应探讨hpv阳性和hpv阴性HNSCC的血管生成机制。
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.