Hatakeyama Hiromitsu, Mizumachi Takatsugu, Sakashita Tomohiro, Kano Satoshi, Homma Akihiro, Fukuda Satoshi
Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060-8638, Japan.
Oncol Rep. 2014 Dec;32(6):2673-9. doi: 10.3892/or.2014.3509. Epub 2014 Sep 22.
High-risk human papillomavirus (HPV) infection is associated with carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC) and patients with HPV-positive tumors have a significantly favorable prognosis. However, the underlying mechanism of this favorable clinical outcome remains unclear. Epithelial-mesenchymal transition (EMT) causes aggressiveness of cancer cells and we investigated the expression of the EMT markers and analyzed their correlation with HPV status and prognosis in order to examine the treatment response of HPV-positive OPSCCs. A total of 79 patients with OPSCC were examined in the present study. All high-risk HPV infections were determined with the multiplex PCR kit from each formalin-fixed paraffin-embedded (FFPE) sample. We performed immunohistochemical staining for E-cadherin and vimentin. Expression of the markers was graded and we statistically analyzed the correlation between tumor, node, metastasis (TNM) stages and prognosis. High-risk HPV-positive tumors were detected in 23 cases. The five‑year survival rate in HPV-positive and -negative tumors was 82.7 and 48.3%, respectively. High E-cadherin expression rate in HPV-negative samples was 76.7% and 43.4% in HPV-positive samples (p=0.007). Vimentin expression did not show a difference between HPV-positive and -negative tumors. HPV-negative patients presented significantly greater heterogeneity of E-cadherin expression compared to HPV-positive patients (p=0.0349). HPV-positive OPSCCs originally lost their epithelial cell phenotype compared with HPV-negative tumors. Therefore, the paradoxical favorable prognosis of HPV-positive OPSCC may be due to the intratumor homogeneity in EMT.
高危型人乳头瘤病毒（HPV）感染与口咽鳞状细胞癌（OPSCC）的致癌作用相关，HPV阳性肿瘤患者的预后明显更好。然而，这种良好临床结果的潜在机制仍不清楚。上皮-间质转化（EMT）导致癌细胞具有侵袭性，我们研究了EMT标志物的表达，并分析了它们与HPV状态及预后的相关性，以检验HPV阳性OPSCC的治疗反应。本研究共检查了79例OPSCC患者。使用来自每个福尔马林固定石蜡包埋（FFPE）样本的多重PCR试剂盒测定所有高危型HPV感染情况。我们对E-钙黏蛋白和波形蛋白进行了免疫组织化学染色。对标志物的表达进行分级，并对肿瘤、淋巴结、转移（TNM）分期与预后之间的相关性进行统计学分析。在23例患者中检测到高危型HPV阳性肿瘤。HPV阳性和阴性肿瘤的五年生存率分别为82.7%和48.3%。HPV阴性样本中E-钙黏蛋白的高表达率为76.7%，HPV阳性样本中为43.4%（p=0.007）。波形蛋白的表达在HPV阳性和阴性肿瘤之间未显示出差异。与HPV阳性患者相比，HPV阴性患者的E-钙黏蛋白表达异质性显著更高（p=0.0349）。与HPV阴性肿瘤相比，HPV阳性OPSCC最初失去了其上皮细胞表型。因此，HPV阳性OPSCC矛盾的良好预后可能归因于EMT中的肿瘤内同质性。
