title: Immunohistochemical analysis of colorectal cancer with gastric phenotype: claudin-18 is associated with poor prognosis.
abstract: Claudin-18 plays a key role in constructing tight junctions, and altered claudin-18 expression has been documented in various human malignancies; however, little is known about the biological significance of claudin-18 in colorectal cancer (CRC). The aim of this study is to investigate the significance of claudin-18 expression in CRC and its association with clinicopathological factors. We performed clinicopathological analysis of claudin-18 expression in a total of 569 CRCs by immunohistochemistry. Moreover, we investigated the association between claudin-18 and various markers including gastric/intestinal phenotype (MUC5AC, MUC6, MUC2 and CD10), CDX2, claudin-3, claudin-4, p53 and Ki-67. Claudin-18 expression was detected in 21 of the 569 CRCs (4%) and was seen exclusively on the cell membrane. Positive expression of claudin-18 showed a significant correlation with positive expression of MUC5AC (P < 0.0001) and negative expression of CDX2 (P= 0.0013). The prognosis of patients with positive claudin-18 expression was significantly poorer than in negative cases (P= 0.0106). Multivariate analysis revealed that T grade, M grade and claudin-18 expression were independent predictors of survival in patients with CRC. We revealed that claudin-18 expression correlates with poor survival in patients with CRC and is associated with the gastric phenotype.
authors.affiliation: Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Matsuda
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sentani
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Noguchi
authors.forename: Takao
authors.initials: T
authors.lastname: Hinoi
authors.forename: Masazumi
authors.initials: M
authors.lastname: Okajima
authors.forename: Keisuke
authors.initials: K
authors.lastname: Matsusaki
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Anami
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Naito
authors.forename: Naohide
authors.initials: N
authors.lastname: Oue
authors.forename: Wataru
authors.initials: W
authors.lastname: Yasui
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D057167:Claudins; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D013270:Stomach / Q000473:pathology; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C486683:CLDN18 protein, human; D057167:Claudins; D008565:Membrane Proteins