title: Vimentin expression is associated with decreased survival in gastric cancer.
abstract: Gastric cancer rich in stromal tissue, such as diffuse-type disease, carries a poor prognosis. In some cancers, expression of vimentin, a mesenchymal maker, is associated with poor survival. The expression of mesenchymal markers such as vimentin is observed after epithelial-mesenchymal transition (EMT), an important initial behavioral change related to the adhesion and migration properties of tumor cells that is required for local tumor invasion. A hallmark of EMT is the loss of E-cadherin. EMT-inducing regulators, including SIP1, Slug, and Twist, repress E-cadherin transcription by interacting with E-cadherin promoter. We investigated the expression of vimentin and EMT-related genes, including SIP1, Slug, and Twist, in frozen cancer tissues and normal tissues by real-time quantitative reverse-transcriptase polymerase chain reaction. Tumor samples were obtained from 106 patients with gastric adenocarcinomas who underwent a gastrectomy. The relation of the expression of these genes to clinicopathological factors and outcomes was studied. Vimentin mRNA was significantly higher in diffuse type compared to intestinal type according to Lauren's classification (p=0.048) and was significantly elevated in patients with recurrent or distant metastatic disease (p=0.049). Immunohistochemically, however, vimentin was detected only in cancer stroma. Twist mRNA expression significantly correlated with tumor depth (p=0.042) and advanced tumor stage (I-II vs. III-IV, p=0.030). E-cadherin immunohistochemical expression was significantly associated with Lauren's histopathological type (p<0.001). Univariate analysis of relapse-free survival showed that tumor depth, lymph node metastasis, Lauren's histopathological type, and vimentin mRNA expression were significant prognostic factors (p<0.001, p=0.013, p=0.011, and p=0.019). On multivariate analysis, vimentin mRNA expression was an independent prognostic factor [hazard ratio (HR)=2.1; 95% confidence interval (CI), 1.0-4.4; p=0.036], coming after tumor depth (HR=9.7; 95%CI, 3.7-24; p<0.001). Vimentin mRNA expression is associated with recurrence or distant metastasis and decreased survival in gastric cancer.
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo, Tokyo 113-8519, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Otsuki
authors.forename: Mikito
authors.initials: M
authors.lastname: Inokuchi
authors.forename: Megumu
authors.initials: M
authors.lastname: Enjoji
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Yoko
authors.initials: Y
authors.lastname: Takagi
authors.forename: Keiji
authors.initials: K
authors.lastname: Kato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamada
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kojima
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D014746:Vimentin / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D014746:Vimentin