Ji Won Kim1, Yangsoon Park2, Jong-Lyel Roh3, Kyung-Ja Cho2, Seung-Ho Choi1, Soon Yuhl Nam1, Sang Yoon Kim1. 1. Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea. 2. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 3. Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea. rohjl@amc.seoul.kr.
Abstract
BACKGROUND: Glucosylceramide synthase (GCS) and P-glycoprotein (P-gp) overexpression are associated with multidrug resistance in several human cancers. This study investigated the prognostic value of GCS and P-gp in oral cavity squamous cell carcinoma (OSCC). METHODS: The association between GCS and P-gp overexpression and clinical outcomes was assessed in 186 human clinical specimens of primary tumors obtained from curative surgery. Immunohistochemistry staining results were scored as high or low for GCS, and positive or negative for P-gp. Univariate and multivariate analyses using the Cox proportional hazards model were conducted to assess the significance of differences in recurrence or survival outcomes between variables. RESULTS: GCS overexpression was observed in 128 (68.8 %) patients and P-gp overexpression in 43 (23.1 %) patients. High GCS expression was significantly correlated with P-gp immunopositivity (P = 0.005). GCS and P-gp overexpression was significantly correlated with cervical nodal metastasis (P < 0.05). Univariate analyses showed that tumor lymphovascular invasion, positive neck lymph nodes, advanced overall TNM stage, high GCS expression, and P-gp immunopositivity were associated with poor locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) (P < 0.05). Multivariate analyses showed that lymphovascular invasion, nodal positivity, and P-gp overexpression remained independent prognostic variables for LRC, DFS, and OS, and that GCS expression was an independent predictor of LRC and DFS (P < 0.05). CONCLUSION: GCS and P-gp expression is associated with poor prognosis, suggesting suitability as novel biomarkers in OSCC.
BACKGROUND:Glucosylceramide synthase (GCS) and P-glycoprotein (P-gp) overexpression are associated with multidrug resistance in several humancancers. This study investigated the prognostic value of GCS and P-gp in oral cavity squamous cell carcinoma (OSCC). METHODS: The association between GCS and P-gp overexpression and clinical outcomes was assessed in 186 human clinical specimens of primary tumors obtained from curative surgery. Immunohistochemistry staining results were scored as high or low for GCS, and positive or negative for P-gp. Univariate and multivariate analyses using the Cox proportional hazards model were conducted to assess the significance of differences in recurrence or survival outcomes between variables. RESULTS:GCS overexpression was observed in 128 (68.8 %) patients and P-gp overexpression in 43 (23.1 %) patients. High GCS expression was significantly correlated with P-gp immunopositivity (P = 0.005). GCS and P-gp overexpression was significantly correlated with cervical nodal metastasis (P < 0.05). Univariate analyses showed that tumor lymphovascular invasion, positive neck lymph nodes, advanced overall TNM stage, high GCS expression, and P-gp immunopositivity were associated with poor locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) (P < 0.05). Multivariate analyses showed that lymphovascular invasion, nodal positivity, and P-gp overexpression remained independent prognostic variables for LRC, DFS, and OS, and that GCS expression was an independent predictor of LRC and DFS (P < 0.05). CONCLUSION:GCS and P-gp expression is associated with poor prognosis, suggesting suitability as novel biomarkers in OSCC.
Authors: Valérie Gouazé; Yong-Yu Liu; Carlton S Prickett; Jing Y Yu; Armando E Giuliano; Myles C Cabot Journal: Cancer Res Date: 2005-05-01 Impact factor: 12.701
Authors: Alfredo Pherez-Farah; Rosa Del Carmen López-Sánchez; Luis Mario Villela-Martínez; Rocío Ortiz-López; Brady E Beltrán; José Ascención Hernández-Hernández Journal: Cancers (Basel) Date: 2022-04-19 Impact factor: 6.575