title: Immunohistochemical features of CD133 expression: association with resistance to chemoradiotherapy in rectal cancer.
abstract: CD133 has been described as a marker for cancer stem cells (CSCs) in colorectal cancer. Additionally, it has been reported that CSCs are resistant to chemoradiotherapy (CRT). After previously observing that CD133 mRNA levels were elevated after CRT in rectal cancer patients, we further investigated CD133 expression in colorectal cancer following CRT using immunohistochemistry. Forty patients with primary colorectal cancers and 50 patients with rectal cancer who had received preoperative CRT followed by surgery were selected. Sections of formalin-fixed, paraffin-embedded specimens were stained for CD133, CK20 and Ki-67. To clarify the change of CD133 protein after irradiation, CD133 protein levels were examined in radiation-treated human colon cancer cell line HT29. We found four distinct patterns of CD133 staining defined by CD133 expression in luminal surface, in intraluminal cells and in cytoplasm. In total, CD133 expression was detected in 27.5% of non-CRT and 70% of CRT specimens. The frequency of CD133 staining in CRT specimens was significantly higher than that of non-CRT specimens. Seven out of 50 CRT specimens exhibited cytoplasmic staining. These cells with cytoplasmic CD133 expression did not express CK20 or Ki-67. The ratio of histopathological responder in cases with CD133 expression in both luminal surface and cytoplasm was significantly lower than that without it (P<0.05). In vitro study showed that CD133 protein was increased in a radiation-dose dependent manner. Further studies clarifying the role of CD133 in tumor re-growth and resistance to conventional CRT in colorectal cancer may assist the development of future cancer therapeutics.
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie 514-8507, Japan. saigusa@clin.medic.mie-u.ac.jp
authors.forename: Susumu
authors.initials: S
authors.lastname: Saigusa
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Toiyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yokoe
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Okugawa
authors.forename: Aya
authors.initials: A
authors.lastname: Kawamoto
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yasuda
authors.forename: Yuki
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujikawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inoue
authors.forename: Chikao
authors.initials: C
authors.lastname: Miki
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism*; D054316:Biomarkers, Pharmacological / Q000032:analysis / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D019008:Drug Resistance, Neoplasm; D006023:Glycoproteins / Q000032:analysis / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D008954:Models, Biological; D010455:Peptides / Q000032:analysis / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D011829:Radiation Dosage; D011836:Radiation Tolerance; D012004:Rectal Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D012333:RNA, Messenger