Overexpression of SIP1 and downregulation of e-cadherin predict delayed neck metastasis in stage I/II oral tongue squamous cell carcinoma after partial glossectomy

Koji Sakamoto, Yorihisa Imanishi, Toshiki Tomita, Masayuki Shimoda, Kaori Kameyama, Katsushi Shibata, Nobuya Sakai, Hiroyuki Ozawa, Seiji Shigetomi, Ryoichi Fujii, Masato Fujii, Kaoru Ogawa

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)612-619
Number of pages8
JournalAnnals of Surgical Oncology
Volume19
Issue number2
DOIs
Publication statusPublished - 2012 Feb

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Glossectomy
Cadherins
Tongue
Squamous Cell Carcinoma
Neck
Down-Regulation
Neoplasm Metastasis
Epithelial-Mesenchymal Transition
Snails
Blood Vessels
Real-Time Polymerase Chain Reaction
Neoplasms
Logistic Models
Immunohistochemistry
Regression Analysis
Cell Line
Messenger RNA

ASJC Scopus subject areas

  • Surgery
  • Oncology

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Overexpression of SIP1 and downregulation of e-cadherin predict delayed neck metastasis in stage I/II oral tongue squamous cell carcinoma after partial glossectomy. / Sakamoto, Koji; Imanishi, Yorihisa; Tomita, Toshiki; Shimoda, Masayuki; Kameyama, Kaori; Shibata, Katsushi; Sakai, Nobuya; Ozawa, Hiroyuki; Shigetomi, Seiji; Fujii, Ryoichi; Fujii, Masato; Ogawa, Kaoru.

In: Annals of Surgical Oncology, Vol. 19, No. 2, 02.2012, p. 612-619.

Research output: Contribution to journalArticle

Sakamoto, Koji ; Imanishi, Yorihisa ; Tomita, Toshiki ; Shimoda, Masayuki ; Kameyama, Kaori ; Shibata, Katsushi ; Sakai, Nobuya ; Ozawa, Hiroyuki ; Shigetomi, Seiji ; Fujii, Ryoichi ; Fujii, Masato ; Ogawa, Kaoru. / Overexpression of SIP1 and downregulation of e-cadherin predict delayed neck metastasis in stage I/II oral tongue squamous cell carcinoma after partial glossectomy. In: Annals of Surgical Oncology. 2012 ; Vol. 19, No. 2. pp. 612-619.
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abstract = "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.",
author = "Koji Sakamoto and Yorihisa Imanishi and Toshiki Tomita and Masayuki Shimoda and Kaori Kameyama and Katsushi Shibata and Nobuya Sakai and Hiroyuki Ozawa and Seiji Shigetomi and Ryoichi Fujii and Masato Fujii and Kaoru Ogawa",
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T1 - Overexpression of SIP1 and downregulation of e-cadherin predict delayed neck metastasis in stage I/II oral tongue squamous cell carcinoma after partial glossectomy

AU - Sakamoto, Koji

AU - Imanishi, Yorihisa

AU - Tomita, Toshiki

AU - Shimoda, Masayuki

AU - Kameyama, Kaori

AU - Shibata, Katsushi

AU - Sakai, Nobuya

AU - Ozawa, Hiroyuki

AU - Shigetomi, Seiji

AU - Fujii, Ryoichi

AU - Fujii, Masato

AU - Ogawa, Kaoru

PY - 2012/2

Y1 - 2012/2

N2 - 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.

AB - 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.

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