title: Wnt3a expression is associated with MMP-9 expression in primary tumor and metastatic site in recurrent or stage IV colorectal cancer.
abstract: BACKGROUND
  The wnt/β-catenin signaling pathway is known to affect in cancer oncogenesis and progression by interacting with the tumor microenvironment. However, the roles of wnt3a and wnt5a in colorectal cancer (CRC) have not been thoroughly studied. In the present study, we investigated the expression of wnt protein and the concordance rate in primary tumor and metastatic sites in CRC. To determine the relationship of wnt proteins with invasion related protein, we also analyzed the association between wnt protein expression and the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor receptor-2 (VEGFR-2).
  
  
  METHODS
  Tumor tissue was obtained from eighty-three paraffin- embedded blocks which were using resected tissue from both the primary tumor and metastatic sites for each patient. We performed immunohistochemical staining for wnt3a, wnt5a, β-catenin, MMP-9 and VEGFR-2.
  
  
  RESULTS
  Wnt3a, wnt5a, β-catenin, and MMP-9 expression was high; the proteins were found in over 50% of the primary tumors, but the prevalence was lower in tissue from metastatic sites. The concordance rates between the primary tumor and metastatic site were 76.2% for wnt5a and 79.4% for wnt3a and β-catenin, but VEGFR-2 was expressed in 67.4% of the metastatic sites even when not found in the primary tumor. Wnt3a expression in primary tumors was significantly associated with lymph node involvement (p = 0.038) and MMP-9 expression in the primary tumor (p = 0.0387), mesenchyme adjacent to tumor (p = 0.022) and metastatic site (p = 0.004). There was no other relationship in the expression of these proteins. Vascular invasion in primary tumor tissue may be a potential prognostic marker for liver metastasis, but no significant association was observed among the wnt protein, MMP-9, and VEGFR-2 for peritoneal seeding. In survival analysis, β-catenin expression was significantly correlated with overall survival (p = 0.05).
  
  
  CONCLUSIONS
  Wnt3a and wnt5a expression had a concordance rate higher than 60% with a high concordance rate between the primary tumor and metastatic site. Wnt3a expression is associated with the expression of MMP-9 in primary tumor tissue adjacent mesenchymal tissue, and at the metastatic site. As a prognostic marker, only β-catenin expression showed significant relation with survival outcome.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul St, Mary's Hospital, 222 Banpo-daero, Seocho-gu, 137-701 Seoul, Korea. angelamd@catholic.ac.kr.
authors.forename: Myung Ah
authors.initials: MA
authors.lastname: Lee
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Park
authors.forename: Si Young
authors.initials: SY
authors.lastname: Rhyu
authors.forename: Seong-Taek
authors.initials: ST
authors.lastname: Oh
authors.forename: Won-Kyoung
authors.initials: WK
authors.lastname: Kang
authors.forename: Hee-Na
authors.initials: HN
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D060509:Wnt3A Protein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C555510:WNT3A protein, human; D060509:Wnt3A Protein; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9