title: WNT-5A, but not matrix metalloproteinase 3 or beta-catenin protein, expression is related to early stages of lip carcinogenesis.
abstract: BACKGROUND
  Oncogenic Wnt/beta-catenin signaling occurs in numerous types of cancers, but little is known about the role of the Wnt protein family member, WNT-5A, in lip carcinogenesis. The aim of this study was to investigate WNT-5A, beta-catenin, and matrix metalloproteinase (MMP)-3 protein expression in actinic cheilitis (AC), and lip squamous cell carcinoma (LSCC).
  
  
  METHODS
  Twenty-one cases of AC, and fifty-one cases of LSCC were analyzed, with normal lip mucosa used as a control. Qualitative and semi-quantitative analyses of WNT-5A, beta-catenin, and MMP-3 immunostaining pattern and cellular distribution were performed.
  
  
  RESULTS
  WNT-5A was observed in more than 50% of the cells, scattered in all layers of AC, in contrast to the absence of immunostaining in normal lip mucosa. AC presented a higher level of WNT-5A expression than LSCC (P = 0.0289, Fisher test), while MMP-3 immunoexpression was statistically more significant in LSCC than in AC (P = 0.0285, Fisher test). Immunolabeling of beta-catenin protein was differentially distributed between samples; the majority of AC cases (61.90%) demonstrated a membranous-cytoplasmic pattern, while a considerable number of LSCC cases (29.41%) revealed a cytoplasmic pattern, instead of the usual membranous pattern.
  
  
  CONCLUSIONS
  The present results suggest that WNT-5A may be an important marker during initial events of AC malignant transformation, in which non-canonical and canonical Wnt/beta-catenin signaling pathways could be involved. Additionally, WNT-5A might recruit other events in LSCC, such as MMP-3 protein synthesis, as its presence is increased in established malignant processes without beta-catenin dependency.
authors.affiliation: Department of Oral Pathology, School of Dentistry, University of São Paulo, São Paulo, Brazil. f.calo@usp.br
authors.forename: Flávia Caló Aquino
authors.initials: FC
authors.lastname: Xavier
authors.forename: Camila Oliveira
authors.initials: CO
authors.lastname: Rodini
authors.forename: Luciana Maria Pedreira
authors.initials: LM
authors.lastname: Ramalho
authors.forename: Andrea
authors.initials: A
authors.lastname: Mantesso
authors.forename: Fabio Daumas
authors.initials: FD
authors.lastname: Nunes
mesh_terms: D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D002613:Cheilitis / Q000209:etiology / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008048:Lip Neoplasms / Q000378:metabolism* / Q000473:pathology; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis*; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000502:physiology; D012189:Retrospective Studies; D015398:Signal Transduction; D013472:Sunlight / Q000009:adverse effects; D051153:Wnt Proteins / Q000096:biosynthesis* / Q000502:physiology; D000071818:Wnt-5a Protein; D051176:beta Catenin / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051176:beta Catenin; D019278:Matrix Metalloproteinase 3