title: Messenger RNA expression of TS and ERCC1 in colorectal cancer and matched liver metastasis.
abstract: 5-fluorouracil (5-FU) and oxaliplatin play important roles in chemotherapy for patients with colorectal cancer. The expression levels of thymidylate synthase (TS) and excision repair cross-complementing factor 1 (ERCC1) have been reported to be prognostic markers for patients with 5-FU/oxaliplatin chemotherapy. The aim of this study was to clarify the association between messenger RNA (mRNA) levels of TS and ERCC1 in primary colorectal cancer and those in corresponding liver metastasis. Formalin-fixed paraffin-embedded tumor specimens of 31 patients with resection for both colorectal cancer and liver metastasis were dissected by laser capture microdissection. After RNA extraction, TS and ERCC1 mRNA levels in both primary tumor and corresponding liver metastasis were measured by real-time reverse transcription-polymerase chain reaction. Both TS and ERCC1 mRNA levels in primary tumors were significantly associated with those in synchronous liver metastases (TS, rs=0.875, p=0.0024; ERCC1, rs=0.835, p=0.0038). TS mRNA levels in primary tumors were also associated with those in metachronous liver metastases (rs=0.659, p=0.0065), but not in ERCC1 (rs=0.319, p=0.19). In both genes, mRNA levels in metachronous liver metastases were higher than those in primary tumors (TS, p=0.0084; ERCC1, p=0.037). However, there was no difference in the TS and ERCC1 mRNA levels between primary tumors and synchronous liver metastasis. The measurement of TS and ERCC1 mRNA levels in primary colorectal cancer can predict those in synchronous liver metastases, but not in metachronous ones.
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan. h-kobayashi.srg2@tmd.ac.jp
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uetake
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Higuchi
authors.forename: Masamichi
authors.initials: M
authors.lastname: Yasuno
authors.forename: Masayuki
authors.initials: M
authors.lastname: Enomoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Iida
authors.forename: Mizutomo
authors.initials: M
authors.lastname: Azuma
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Mori
authors.forename: Akiko
authors.initials: A
authors.lastname: Omori
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Lenz
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Danenberg
authors.forename: Peter V
authors.initials: PV
authors.lastname: Danenberg
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003082:Colectomy; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006498:Hepatectomy; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000556:secondary / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D012333:RNA, Messenger / Q000032:analysis*; D013940:Thymidylate Synthase / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D012333:RNA, Messenger; D000077150:Oxaliplatin; D013940:Thymidylate Synthase; C071447:ERCC1 protein, human; D004720:Endonucleases; D002955:Leucovorin; D005472:Fluorouracil