Post-Graduation in Health Science, Faculty of Medicine (FM), Federal University of Mato Grosso (UFMT), Mato Grosso, MT 78060-900, Brazil ; Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK ; Henry Wellcome Laboratory, University of Liverpool, 1st Floor, Nuffield Building, Liverpool L69 3GE, UK.
Post-Graduation in Health Science, Faculty of Medicine (FM), Federal University of Mato Grosso (UFMT), Mato Grosso, MT 78060-900, Brazil.
Infect Agent Cancer. 2014 Apr 21;9:13. doi: 10.1186/1750-9378-9-13. eCollection 2014.
Human papillomavirus (HPV) is often present in oropharyngeal cancers. Head and neck tumors have been examined for other molecular markers including p53 and annexin A1 (ANXA1). Here, we investigated the prevalence of HPV and its relationship with p53 and ANXA1 in patients with oropharyngeal cancer.
We have analyzed tumor and adjacent mucosa from 22 patients with squamous cell carcinoma of the oropharynx in addition to samples of the oropharyngeal epithelium in subjects without cancer. We evaluated the presence of the HPV (subtypes 16/18 and 31/33) by chromogenic in situ hybridization. Additionally, we used immunofluorescence to examine the expression of p16, p53, ANXA1 and the phosphorylation of the ANXA1 residues Ser27 (ANXA1-SER) and Tyr21 (ANXA1-TYR).
We have detected the presence of HPV genome in 59% of the 22 tumors. Of those, 92% were also positive for p16 immunostaining. Furthermore, we demonstrated a reduction in the expression of p53 in HPV + compared to HPV- tumors. Also, a reduction was observed in the expression of ANXA1 in tumors compared to epithelium from the margins and from controls. We also noted a reduction in ANXA1-TYR in tumors. However, the expression of both ANXA1 and ANXA1-SER were elevated in the margins of the HPV + versus HPV- tumors.
Our results confirm a high prevalence of HPV in oropharyngeal cancer and a reduction in p53 expression in HPV + tumors. We observed a hypoexpression of ANXA1 and ANXA1-TYR in oropharyngeal cancer. The increase in ANXA1-SER in the margins of HPV + tumors suggests that the epithelium in these cases had been activated by an infectious agent. Those findings indicate that ANXA1 and its phosphorylated forms can play important roles in the response to HPV infection and the carcinogenesis of the oropharynx.
人乳头瘤病毒（HPV）常存在于口咽癌中。已经对头颈部肿瘤进行了其他分子标志物的检查，包括 p53 和膜联蛋白 A1（ANXA1）。在这里，我们研究了 HPV 的流行情况及其与口咽癌患者 p53 和 ANXA1 的关系。
我们分析了 22 例口咽鳞状细胞癌患者的肿瘤和相邻黏膜，以及无癌症患者的口咽上皮样本。我们通过显色原位杂交评估 HPV（16/18 和 31/33 亚型）的存在。此外，我们使用免疫荧光法检查 p16、p53、ANXA1 以及 ANXA1 残基 Ser27（ANXA1-SER）和 Tyr21（ANXA1-TYR）的磷酸化。
我们在 22 个肿瘤中有 59%检测到 HPV 基因组。其中，92%的肿瘤 p16 免疫染色也呈阳性。此外，我们发现在 HPV+肿瘤中 p53 的表达减少。此外，与边缘和对照上皮相比，肿瘤中 ANXA1 的表达也减少。我们还注意到肿瘤中 ANXA1-TYR 的减少。然而，在 HPV+肿瘤的边缘，ANXA1 和 ANXA1-SER 的表达都升高。
我们的结果证实了 HPV 在口咽癌中的高流行率以及 HPV+肿瘤中 p53 表达的减少。我们观察到口咽癌中 ANXA1 和 ANXA1-TYR 的低表达。HPV+肿瘤边缘的 ANXA1-SER 增加表明这些情况下的上皮细胞已被感染剂激活。这些发现表明，ANXA1 及其磷酸化形式可能在 HPV 感染反应和口咽癌发生中发挥重要作用。
