title: CD133 expression in well-differentiated pancreatic neuroendocrine tumors: a potential predictor of progressive clinical courses.
abstract: The present study aimed to elucidate whether the stemness molecule, CD133, is expressed in well-differentiated pancreatic neuroendocrine tumors (PanNETs; World Health Organization grades 1 and 2) and establish its clinical relevance using 2 separate cohorts. In the first series (n = 178) in which tissue microarrays were available, immunohistochemistry revealed that CD133 was expressed in 14 cases (8%). CD133+ PanNETs had higher TNM stages (P < .01), more frequent lymphovascular invasion (P = .01), and higher recurrence rates (P = .01). In the second cohort (n = 56), the expression of CD133 and CK19 was examined in whole tissue sections. CD133 and CK19 were positive in 10 (18%) and 36 (64%) cases, respectively. CD133 expression correlated with higher pT scores (P < .01), the presence of microscopic venous infiltration (P = .03), and shorter disease-free periods (P < .01). When cases were divided into grade 1 and 2 neoplasms, patients with CD133+ PanNET continued to have shorter disease-free periods than did those with CD133- tumors in both groups (P < .01 and P = .02, respectively). Although CK19+ cases had shorter disease-free periods than did CK19- cases in the whole cohort (P = .02), this difference was less apparent in subanalyses of grade 1 and 2 cases. CD133 expression also appeared to be an independent predictive factor for tumor recurrence in a multivariate analysis (P = .018). The CD133 phenotype was identical between primary and metastatic foci in 17 of 18 cases from which tissues of metastatic deposits were available. In conclusion, the combination of CD133 phenotyping and World Health Organization grading may assist in stratifying patients in terms of the risk of progressive clinical courses.
authors.affiliation: Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: sakaiyasuhiro@gaia.eonet.ne.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Sakai
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. Electronic address: smhong28@gmail.com.
authors.forename: Seung-Mo
authors.initials: SM
authors.lastname: Hong
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. Electronic address: soyan21@gmail.com.
authors.forename: Soyeon
authors.initials: S
authors.lastname: An
authors.affiliation: Department of Pathology, Korea University Anam Hospital, Korea University College of Medicine, Seoul 02841, Republic of Korea. Electronic address: lepetit80@hanmail.net.
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Tissue Engineering Laboratories (BIOTEC), Technische Universität Dresden, Dresden 01307, Germany. Electronic address: denis.corbeil@biotec.tu-dresden.de.
authors.forename: Denis
authors.initials: D
authors.lastname: Corbeil
authors.affiliation: Tissue Engineering Laboratories (BIOTEC), Technische Universität Dresden, Dresden 01307, Germany. Electronic address: jana.karbanova@biotec.tu-dresden.de.
authors.forename: Jana
authors.initials: J
authors.lastname: Karbanová
authors.affiliation: Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: otanikyo@med.kobe-u.ac.jp.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Otani
authors.affiliation: Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: kofujikura@gmail.com.
authors.forename: Kohei
authors.initials: K
authors.lastname: Fujikura
authors.affiliation: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. Electronic address: mtsong21c@naver.com.
authors.forename: Ki-Byung
authors.initials: KB
authors.lastname: Song
authors.affiliation: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. Electronic address: drksc@amc.seoul.kr.
authors.forename: Song Cheol
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: bokuakkey70033@gmail.com.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Akita
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: yos_3n@hotmail.com.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Nanno
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: tymhr@me.com.
authors.forename: Hirochika
authors.initials: H
authors.lastname: Toyama
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: fukumoto@med.kobe-u.ac.jp.
authors.forename: Takumi
authors.initials: T
authors.lastname: Fukumoto
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: yonson@med.kobe-u.ac.jp.
authors.forename: Yonson
authors.initials: Y
authors.lastname: Ku
authors.affiliation: Department of Pathology, Hyogo Cancer Center, Akashi 673-8558, Japan. Electronic address: thirose@hp.pref.hyogo.jp.
authors.forename: Takanori
authors.initials: T
authors.lastname: Hirose
authors.affiliation: Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: tomitoh@med.kobe-u.ac.jp.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Itoh
authors.affiliation: Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: yohzen@med.kobe-u.ac.jp.
authors.forename: Yoh
authors.initials: Y
authors.lastname: Zen
mesh_terms: D000071916:AC133 Antigen / Q000032:analysis*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002454:Cell Differentiation; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D053539:Keratin-19 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000276:immunology* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D010641:Phenotype; D013997:Time Factors; D046888:Tissue Array Analysis
chemical_list: D000071916:AC133 Antigen; D014408:Biomarkers, Tumor; D053539:Keratin-19; C000606023:PROM1 protein, human
keywords: CD133; CK19; MIB-1; Neuroendocrine tumor; Prognosis; Stem cell