title: Expression of the KAI1 metastasis suppressor gene in non-metastatic versus metastatic human colorectal cancer.
abstract: BACKGROUND
  The importance of KAI1 to colorectal cancer (CRC) progression is unclear, with conflicting data regarding changes in KAI1 expression during tumour progression.
  
  
  METHODS
  In situ hybridisation and immunohistochemistry, with a semiquantitative scoring system, were used to assess KAI1 mRNA and protein levels, respectively, in normal colon samples (43), and non-metastatic (24) or metastatic (33) primary cancers, and liver metastases (48).
  
  
  RESULTS
  There was significant loss of KAI1 mRNA and protein staining in non-metastatic primary tumours versus normal tissues (Bonferroni, p < 0.05) but levels recovered to near normal in metastatic primary tumours and liver metastases. Increased KAI1 expression significantly correlated with distant metastases (Mann-Whitney, p = 0.0001, mRNA; p = 0.033, protein), cancer-specific survival (Cox regression analysis p = 0.0002, mRNA; 0.0493, protein) and overall patient survival (p = 0.0001, mRNA). Multivariate analysis (Cox proportional hazards model) confirmed high KAI1 mRNA expression was an independent prognostic indicator of distant metastasis (p < 0.0001), cancer-specific survival (p < 0.0001) and overall patient survival (p < 0.0001).
  
  
  CONCLUSIONS
  These data indicate a complex relationship between KAI1 and progression of human CRC, in which expression is reduced in localised primary tumours, but regained in disease associated with metastasis.
authors.affiliation: Department of Surgery, Prince of Wales Hospital, Randwick, NSW 2031, Australia. j.yang@unsw.edu.au
authors.forename: Jia-Lin
authors.initials: JL
authors.lastname: Yang
authors.forename: Paul
authors.initials: P
authors.lastname: Jackson
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Russell
authors.forename: Boban
authors.initials: B
authors.lastname: Markovic
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Crowe
mesh_terms: D000704:Analysis of Variance; D015703:Antigens, CD; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051861:Kangai-1 Protein; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D016612:Paraffin Embedding; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015996:Survival Rate
chemical_list: D015703:Antigens, CD; C497688:CD82 protein, human; D051861:Kangai-1 Protein; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger