title: Cancer Stem Cell Markers in Eyelid Sebaceous Gland Carcinoma: High Expression of ALDH1, CD133, and ABCG2 Correlates With Poor Prognosis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Namju
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea Department of Ophthalmology, Seoul Municipal Government-Seoul National University Boramae Hospital, Seoul, Korea.
authors.forename: Ho-Kyung
authors.initials: HK
authors.lastname: Choung
authors.affiliation: Department of Ophthalmology, Hallym University Sacred Hospital, Pyongchon, Korea.
authors.forename: Min Joung
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Sang In
authors.initials: SI
authors.lastname: Khwarg
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea Department of Pathology, Seoul Municipal Government-Seoul National University Boramae Hospital, Seoul, Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Kim
mesh_terms: D000071916:AC133 Antigen; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D018266:Adenocarcinoma, Sebaceous / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000080924:Aldehyde Dehydrogenase 1 Family; D015703:Antigens, CD / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000378:metabolism; D005142:Eyelid Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010455:Peptides; D011379:Prognosis; D050697:Retinal Dehydrogenase / Q000096:biosynthesis*; D012189:Retrospective Studies; D012626:Sebaceous Gland Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: C116614:ABCG2 protein, human; D000071916:AC133 Antigen; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D007527:Isoenzymes; D009363:Neoplasm Proteins; C000606023:PROM1 protein, human; D010455:Peptides; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase
keywords: cancer stem cell; metastasis; sebaceous carcinoma