Lefevre Marine, Rousseau Alexandra, Rayon Thomas, Dalstein Véronique, Clavel Christine, Beby-Defaux Agnès, Pretet Jean-Luc, Soussan Patrick, Polette Myriam, Lacau Saint Guily Jean, Birembaut Philippe
Laboratoire d'Anatomie Pathologique, Hôpital Tenon, 4, rue de la Chine, Université Pierre et Marie Curie Paris 6,75050 Paris, France.
AP-HP Hôpital Saint Antoine, URC-Est, 184 rue du Faubourg Saint Antoine, Université Pierre et Marie Curie Paris 6, 75012 Paris, France.
Br J Cancer. 2017 Jan;116(3):362-369. doi: 10.1038/bjc.2016.434. Epub 2017 Jan 10.
Human Papillomavirus (HPV) infection is recognised as aetiological factor of carcinogenesis in oropharyngeal squamous cell carcinomas (OPC). HPV-related OPC respond better to treatments and have a significantly favourable outcome. Epithelial to mesenchymal transition (EMT) implicated in tumour invasion, is a hallmark of a poor prognosis in carcinomas.
We have studied the relationship of EMT markers (E-cadherin, β-catenin and vimentin) with HPV infection (DNA and E6/E7 mRNA detection), p16 expression and survival outcomes in a cohort of 296 patients with OPC.
Among the 296 OPSSC, 26% were HPV positive, 20.3% had overt EMT (>25% of vimentin positive tumour cells). Lower E-cadherin expression was associated with a higher risk of distant metastasis in univariate (P=0.0110) and multivariate analyses (hazard ratios (HR)=6.86 (1.98; 23.84)). Vimentin expression tends towards worse metastasis-free survival (MFS; HR=2.53 (1.00; 6.41)) and was an independent prognostic factor of progression-free survival (HR=1.55 (1.03; 2.34)).
There was a non significant association of EMT with HPV status. This may be explained by a mixed subpopulation of patients HPV positive with associated risk factors (HPV, tobacco and alcohol). Thus, the detection of EMT in OPC represents another reliable approach in the prognosis and the management of OPC whatever their HPV status.
人乳头瘤病毒（HPV）感染被认为是口咽鳞状细胞癌（OPC）致癌的病因。与HPV相关的OPC对治疗反应更好，预后明显更佳。上皮-间质转化（EMT）与肿瘤侵袭有关，是癌症预后不良的标志。
我们研究了296例OPC患者队列中EMT标志物（E-钙黏蛋白、β-连环蛋白和波形蛋白）与HPV感染（DNA和E6/E7 mRNA检测）、p16表达及生存结果之间的关系。
在296例OPSSC中，26%为HPV阳性，20.3%有明显的EMT（波形蛋白阳性肿瘤细胞>25%）。在单因素分析（P=0.0110）和多因素分析中，较低的E-钙黏蛋白表达与远处转移风险较高相关（风险比（HR）=6.86（1.98；23.84））。波形蛋白表达倾向于无转移生存期（MFS）更差（HR=2.53（1.00；6.41）），并且是无进展生存期的独立预后因素（HR=1.55（1.03；2.34））。
EMT与HPV状态之间存在不显著的关联。这可能是由于HPV阳性且伴有相关风险因素（HPV、烟草和酒精）的患者亚群混合所致。因此，无论HPV状态如何，OPC中EMT的检测代表了OPC预后和管理的另一种可靠方法。
