Induction of epithelial-mesenchymal transition and loss of podoplanin expression are associated with progression of lymph node metastases in human papillomavirus-related oropharyngeal carcinoma
Induction of epithelial-mesenchymal transition and loss of podoplanin expression are associated with progression of lymph node metastases in human papillomavirus-related oropharyngeal carcinoma
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DOI：
10.1111/his.12496
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发表时间：
2015-05-01
期刊：
影响因子：
6.4
通讯作者：
Yoshizaki, Tomokazu
中科院分区：
文献类型：
--
作者：
Wakisaka, Naohiro;Yoshida, Shinya;Yoshizaki, Tomokazu
目的检测口咽鳞癌组织中人乳头瘤病毒（HPV）感染状况、podoplanin和上皮间质转化（EMT）标志物的表达及淋巴管计数（LVC），方法和结果对53例OPSCC标本进行HPV感染状态和podoplanin、EMT等蛋白表达的检测免疫组织化学标记。E-cadherin阴性和波形蛋白阳性的标本被定义为EMT阳性。22例OPSCC为HPV阳性。HPV阳性肿瘤患者的淋巴结状态有显著进展（P=0.0475）。HPV阳性病例podoplanin表达显著降低（P=0.0016），EMT阳性率更高（P=0.0172）。Podoplanin阴性病例和EMT阳性病例的淋巴结状态比各自的对应者明显更晚期（分别为P=0.0082和P 0.0186）。LVC与HPV和淋巴结状态均不相关。多因素分析显示HPV感染是一个独立的标志物，较长的疾病特异性survival（P=0.014）。结论HPV阳性OPSCC与podoplanin表达的损失和EMT诱导，导致进展的淋巴结状态。导致HPV阳性OPSCC患者预后改善的机制需要阐明，因为这与淋巴结转移的侵袭性表型不一致。
Aims To examine human papillomavirus (HPV) status, the expression of podoplanin and epithelial-mesenchymal transition (EMT) markers and lymphatic vessel counts (LVC) in oropharyngeal squamous cell carcinoma (OPSCC) tissues, and to evaluate whether these factors were associated with survival and nodal status.Methods and results A total of 53 OPSCC specimens were evaluated for HPV status and expression of proteins such as podoplanin and EMT markers by immunohistochemistry. E-cadherin-negative and vimentin-positive specimens were defined as EMT-positive. Twenty-twoOPSCCs were HPV-positive. There was significant progression of nodal status in patients with HPV-positive tumours (P=0.0475). HPV-positive cases had significantly lower expression of podoplanin (P=0.0016) and were more frequently EMT-positive (P=0.0172). Podoplanin-negative cases and EMT-positive cases showed significantly more advanced nodal status than their respective counterparts (P=0.0082 and P0.0186, respectively). LVC correlated with neither HPV nor nodal status. Multivariate analyses revealed that HPV infection was an independent marker of longer disease-specific survival (P=0.014).Conclusions HPV-positivity in OPSCC was associated with loss of podoplanin expression and with EMT induction, which resulted in progression of nodal status. The mechanisms leading to an improved prognosis in HPV-positive OPSCC patients requires elucidation, as this is inconsistent with the aggressive phenotype with lymph node metastases.