Epithelial-mesenchymal transition in human papillomavirus‑positive and -negative oropharyngeal squamous cell carcinoma

Hatakeyama,Hiromitsu; Mizumachi,Takatsugu; Sakashita,Tomohiro; Kano,Satoshi; Homma,Akihiro; Fukuda,Satoshi

doi:10.3892/or.2014.3509

Epithelial-mesenchymal transition in human papillomavirus‑positive and -negative oropharyngeal squamous cell carcinoma

Authors:
- Hiromitsu Hatakeyama
- Takatsugu Mizumachi
- Tomohiro Sakashita
- Satoshi Kano
- Akihiro Homma
- Satoshi Fukuda
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Affiliations: Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060-8638, Japan
Published online on: September 22, 2014 https://doi.org/10.3892/or.2014.3509
Pages: 2673-2679

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Abstract

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.

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