Impact of p16 status on pro- and anti-angiogenesis factors in head and neck cancers

Abstract

Background:Head and neck cancers (HNC) are aggressive tumours. Overexpression of p16 in HNC correlates with human papilloma virus (HPV)-associated HNC that carry a better prognosis than HPV-negative tumours. Angiogenesis is an important factor in tumour progression. Our aim was to dissect the impact of p16 expression on angiogenesis factors in HNC.Methods:Eighteen newly diagnosed HNC patients and controls were analysed. Eleven pro- and anti-angiogenesis factors were quantified using multiplex ELISA in HNC patients and controls. Angiogenesis factors were analysed in tumour tissue using immunohistochemistry.Results:Circulating levels of endostatin (anti-angiogenesis factor) were higher in the HNC group compared with healthy donors. Interestingly, the pro-angiogenesis factors angiopoietin-1 and vascular endothelial growth factor (VEGF) were significantly higher in patients with p16-negative compared with p16-positive HNC. Moreover, the major source of VEGF in p16-positive HNC tissue was tumour stromal cells. In contrast, both tumour cells and stromal cells expressed VEGF in p16-negative tissue.Conclusions:We show that p16-negative tumours associate with increased circulating levels of pro-angiogenic VEGF and angiopoietin-1. Tissue expression of VEGF differs between p16-positive and p16-negative tumours. These findings may explain differences in the biological behaviour of p16-positive and p16-negative HNC. Better understanding of mechanisms by which the p16 status influences tumour angiogenesis may guide the development of targeted therapies.

Gene Expression Comparison Between the Primary Tumor and its Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma: A Pilot Study

“…This is in accordance with two recent studies that showed EGFR alterations more commonly present in HPV-negative tumors (19) and the anti-EGFR antibody panitumumab possibly more effective in HPV-negative patients (20). VEGF binds to vascular endothelial growth factor receptor 2 (VEGFR-2) and VRGFR-3, and is the molecule primarily responsible for lymphangiogenesis and angiogenesis (5). In the current study, VEGF is over-expressed in 52.9% of the primary tumors, but even more in the associated lymph node metastasized tumors.…”

“…Thus, the aim of this study was to compare the expression of genes implicated in different aspects of HNSCC carcinogenesis between the primary tumor and the corresponding lymph node metastases. These include the epidermal growth factor receptor (EGFR), a well-known receptor tyrosine kinase (4), the vascular endothelial growth factor (VEGF) implicated in lymphangiogenesis and angiogenesis (5), claudin7 (6) and maspin, (7) two major tumor cell-environment interaction factors, survivin (8), an anti-apoptotic regulator, and squamous cell carcinoma antigen (SCCA) (9), a serological marker of squamous cell carcinomas.…”

Synergistic effects of the combination of 5-Aza‑CdR and suberoylanilide hydroxamic acid on the anticancer property of pancreatic cancer

“…The gene encoding p16 is mutated or downregulated in several cancer cells (38)(39)(40). However, breast carcinoma progression has been related to overexpression of p16 (41), and this has been reported in head and neck squamous carcinoma (42), in prostate carcinoma (43). Here, we detected TP53 and p16 mRNA and protein expression after treatment of 5-Aza-CdR and SAHA.…”

T1 high-grade bladder carcinoma outcome: the role of p16, topoisomerase-II α , survivin, and E-cadherin

“…The gene encoding p16 is mutated or downregulated in several cancer cells. Breast carcinoma progression has been related to overexpression of p16 [14], and this has been reported in head and neck squamous carcinoma [15], in prostate carcinoma [16], and also in aggressive subtypes of bladder carcinoma [17][18][19][20].…”