title: High expression of Twist is associated with tumor aggressiveness and poor prognosis in patients with renal cell carcinoma.
abstract: OBJECTIVE
  Twist has been reported to play crucial roles for malignant aggressiveness; however, detailed pathological significance of Twist in renal cell carcinoma (RCC) is not fully understood. The present study was to clarify clinical significance and molecular functions of Twist in patients with RCC.
  
  
  METHODS
  Twist expression was examined by immunohistochemical techniques in 156 formalin-fixed specimens. Cell proliferation, angiogenesis, and apoptosis were measured as the percentage of Ki-67-positive cells (proliferation index, PI), CD31-stained vessels (microvessel density, MVD), and TUNEL-positive cells (apoptotic index, AI). In addition, semi-quantification of matrix metalloproteinase (MMP)-2 was performed. Macrophages were identified with anti-CD68 antibody, and the tumor associated macrophage (TAM) density was calculated as CD68-positive cells per high-power field.
  
  
  RESULTS
  Twist expression was positively associated with grade, pT stage, and metastasis (p<0.001). We also noticed that its expression was considerably higher in cancer cells of sarcomatoid RCC and in those at the edge of the tumors. Twist expression was positively correlated with PI, MVD, MMP2 expression, and TAM density (P<0.001), but not with AI, and MMP-2 expression and TAM density were independently correlate by multi-variate analyses. Kaplan-Meir survival curves showed high Twist expression was a worse predictor for cause-specific survival (P<0.001).
  
  
  CONCLUSIONS
  Twist plays important roles in tumor growth, progression, and survival in patients with RCC patients. Such pathological mechanisms are significantly associated with increased cancer cell proliferation, angiogenesis, MMP2 expression, and macrophage recruitment. These findings are important information for discussion of treatment and observation strategies in these patients.
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences Nagasaki, Japan.
authors.forename: Kojiro
authors.initials: K
authors.lastname: Ohba
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences Nagasaki, Japan.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Miyata
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences Nagasaki, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsuo
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences Nagasaki, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Asai
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences Nagasaki, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Mitsunari
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences Nagasaki, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shida
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences Nagasaki, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kanda
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences Nagasaki, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Sakai
mesh_terms: D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D009687:Nuclear Proteins / Q000032:analysis / Q000096:biosynthesis*; D011379:Prognosis; D016016:Proportional Hazards Models; D051879:Twist-Related Protein 1 / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1
keywords: Twist; angiogenesis; cell proliferation; macrophage; matrix metalloproteinases; renal cell carcinoma