Namju Kim1, Ho-Kyung Choung2, Min Joung Lee3, Sang In Khwarg4, Ji Eun Kim5. 1. Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Korea. 2. Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea Department of Ophthalmology, Seoul Municipal Government-Seoul National University Boramae Hospital, Seoul, Korea. 3. Department of Ophthalmology, Hallym University Sacred Hospital, Pyongchon, Korea. 4. Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea. 5. Department of Pathology, Seoul National University College of Medicine, Seoul, Korea Department of Pathology, Seoul Municipal Government-Seoul National University Boramae Hospital, Seoul, Korea.
Abstract
PURPOSE: To investigate the expression of cancer stem cell (CSC) marker proteins in eyelid sebaceous gland carcinoma and evaluate the clinical significance. METHODS: Archival tissue blocks from 50 cases of eyelid sebaceous gland carcinoma were tested via immunohistochemistry for 16 putative CSC markers. Levels of protein expression were analyzed alongside various clinicopathologic parameters such as metastasis-free survival time. RESULTS: Ten patients (20%) showed nodal or distant metastasis during the follow-up period (median, 35.2 months; range, 1-128 months) without any mortality in our series. Among the 16 markers, ALDH1, CD44, CD133, ABCG2, Sox4, Sox9, and slug were selected for candidates of CSC markers because they were frequently and predominantly found in the tumor cells compared with control tarsus cells, which showed negative or very low expression. Univariate analysis revealed that ALDH1, CD133, and ABCG2 were significantly associated with metastasis; patients with ALDH1- or CD133-positive tumors developed metastasis more frequently than patients with tumors that were negative for these markers (log-rank test, P = 0.014, P = 0.013, respectively), and diffuse expression of ABCG2 was associated with significantly shorter metastasis-free survival (log-rank test, P = 0.010). Multivariate Cox proportional hazard model revealed that ALDH1 (hazard ratio [HR] = 5.682, P = 0.038) was significantly associated with metastasis. CONCLUSIONS: Development of metastasis in eyelid sebaceous gland carcinoma might be attributed to increased number of CSCs or acquisition of dedifferentiated phenotype. Our findings suggest that CSCs are involved in the disease progression of eyelid sebaceous gland carcinoma, and in particular, expression of ALDH1 is a predictor of a poor outcome. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.
PURPOSE: To investigate the expression of cancer stem cell (CSC) marker proteins in eyelid sebaceous gland carcinoma and evaluate the clinical significance. METHODS: Archival tissue blocks from 50 cases of eyelid sebaceous gland carcinoma were tested via immunohistochemistry for 16 putative CSC markers. Levels of protein expression were analyzed alongside various clinicopathologic parameters such as metastasis-free survival time. RESULTS: Ten patients (20%) showed nodal or distant metastasis during the follow-up period (median, 35.2 months; range, 1-128 months) without any mortality in our series. Among the 16 markers, ALDH1, CD44, CD133, ABCG2, Sox4, Sox9, and slug were selected for candidates of CSC markers because they were frequently and predominantly found in the tumor cells compared with control tarsus cells, which showed negative or very low expression. Univariate analysis revealed that ALDH1, CD133, and ABCG2 were significantly associated with metastasis; patients with ALDH1- or CD133-positive tumors developed metastasis more frequently than patients with tumors that were negative for these markers (log-rank test, P = 0.014, P = 0.013, respectively), and diffuse expression of ABCG2 was associated with significantly shorter metastasis-free survival (log-rank test, P = 0.010). Multivariate Cox proportional hazard model revealed that ALDH1 (hazard ratio [HR] = 5.682, P = 0.038) was significantly associated with metastasis. CONCLUSIONS: Development of metastasis in eyelid sebaceous gland carcinoma might be attributed to increased number of CSCs or acquisition of dedifferentiated phenotype. Our findings suggest that CSCs are involved in the disease progression of eyelid sebaceous gland carcinoma, and in particular, expression of ALDH1 is a predictor of a poor outcome. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.
Entities:
Keywords:
cancer stem cell; metastasis; sebaceous carcinoma