title: Quantitative analysis of MUC1 and MUC5AC mRNA in pancreatic juice for preoperative diagnosis of pancreatic cancer.
abstract: Pancreatic juice is a promising type of diagnostic sample for pancreatic cancer, and members of the mucin (MUC) family are diagnostic candidates. To evaluate the utility of MUC family members as diagnostic markers, we measured MUC mRNA expression in pancreatic tissues and pancreatic juice obtained from patients with different pancreatic diseases as well as in pancreatic cancer cell lines by real-time PCR. Furthermore, to support the possibility of early diagnosis by quantification of MUC1 and MUC5AC, immunohistochemistry and microdissection-based quantitative analysis of mRNA were carried out. There was no significant correlation between MUC1 and MUC5AC expression in cell lines. When beta-actin was used as a reference gene, median MUC1 and MUC5AC mRNA expression levels were remarkably greater in tumoral tissues than in non-tumoral tissues, but median MUC4 and MUC6 mRNA expression levels were not. Receiver operating characteristic curve analysis showed that quantitative analysis of MUC1 and MUC5AC mRNA in pancreatic juice is better diagnostic modality than that of MUC4 and MUC6 mRNA. Immunohistochemistry showed that MUC1 and MUC5AC were highly expressed in invasive ductal carcinomas (IDC) and moderately expressed in high-grade pancreatic intraepithelial neoplasia (PanIN); no staining was observed in normal ducts. Analysis of cells isolated by microdissection showed stepwise upregulation of MUC1 and MUC5AC in the development of high-grade PanIN to IDC. Our results suggest that MUC1 and MUC5AC are upregulated stepwise in pancreatic carcinogenesis and that quantitative assessment of MUC1 and MUC5AC mRNA in pancreatic juice has high potential for preoperative diagnosis of pancreatic cancer.
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kenoki
authors.initials: K
authors.lastname: Ohuchida
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mizumoto
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamada
authors.forename: Kei
authors.initials: K
authors.lastname: Fujii
authors.forename: Nami
authors.initials: N
authors.lastname: Ishikawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konomi
authors.forename: Eishi
authors.initials: E
authors.lastname: Nagai
authors.forename: Koji
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Masazumi
authors.initials: M
authors.lastname: Tsuneyoshi
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry; D055271:Mucin 5AC; D018396:Mucin-1 / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D009077:Mucins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D010189:Pancreatic Juice / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000175:diagnosis*; D016133:Polymerase Chain Reaction; D011300:Preoperative Care; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D018396:Mucin-1; D009077:Mucins; D012333:RNA, Messenger