Overexpression of SIP1 and Downregulation of E-cadherin Predict Delayed Neck Metastasis in Stage I/II Oral Tongue Squamous Cell Carcinoma After Partial Glossectomy

• Published in: Annals of surgical oncology 2012-02, Vol.19 (2), p.612-619
• Main Authors: Sakamoto, Koji, Imanishi, Yorihisa, Tomita, Toshiki, Shimoda, Masayuki, Kameyama, Kaori, Shibata, Katsushi, Sakai, Nobuya, Ozawa, Hiroyuki, Shigetomi, Seiji, Fujii, Ryoichi, Fujii, Masato, Ogawa, Kaoru
• Format: Article
• Language: English
• Subjects: Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Blotting, Western; Cadherins - genetics; Cadherins - metabolism; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - surgery; Down-Regulation; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Neoplastic; Glossectomy; Head and Neck Oncology; Humans; Immunoenzyme Techniques; Lymph Node Excision; Lymphatic Metastasis; Male; Medical Records; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Oncology; Prognosis; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Surgery; Surgical Oncology; Tongue Neoplasms - genetics; Tongue Neoplasms - metabolism; Tongue Neoplasms - surgery; Tumor Cells, Cultured
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-011-2052-1

Background Patients with clinical stage I/II (T1–2N0M0) oral tongue squamous cell carcinoma (TSCC) usually undergo partial glossectomy alone. However, 14–48% of them develop delayed neck metastasis (DNM), which may lead to an unfavorable course. Recently epithelial-to-mesenchymal transition (EMT) has been thought to play a crucial role in cancer metastasis. The present study aimed to examine the associations of EMT-involved molecular factors and clinicopathological factors with DNM in stage I/II TSCC. Methods mRNA expression levels of E-cadherin and its transcriptional repressors (snail, SIP1, and twist) in 7 head and neck squamous cell carcinoma (HNSCC) cell lines were evaluated by quantitative real-time PCR. Clinicopathological parameters and immunohistochemical expressions of E-cadherin and its repressors were examined in surgical specimens of 37 stage I/II TSCC patients who underwent partial glossectomy alone. Results In HNSCC cells, E-cadherin expression was inversely correlated with SIP1 expression ( P  = 0.023). Univariate analysis of immunohistochemistry showed that overexpression of SIP1 and loss of E-cadherin were significantly correlated with DNM, although no inverse correlation was found between E-cadherin and its repressors. Multiple logistic regression analysis including clinicopathological and molecular factors revealed that overexpression of SIP1 ( P  = 0.005), loss of E-cadherin ( P  = 0.046), and vascular invasion ( P  = 0.024) were independently correlated with DNM. Conclusions These results suggest that development of DNM in stage I/II TSCC is closely related to induction of EMT in primary tumor cells. Especially, SIP1 and E-cadherin are considered to be the possible markers for selecting patients at high risk of DNM.