PMID- 19473452 OWN - NLM STAT- MEDLINE DCOM- 20091215 LR - 20161125 IS - 1600-0714 (Electronic) IS - 0904-2512 (Linking) VI - 38 IP - 9 DP - 2009 Oct TI - WNT-5A, but not matrix metalloproteinase 3 or beta-catenin protein, expression is related to early stages of lip carcinogenesis. PG - 708-15 LID - 10.1111/j.1600-0714.2009.00756.x [doi] AB - 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. FAU - Xavier, Flavia Calo Aquino AU - Xavier FC AD - Department of Oral Pathology, School of Dentistry, University of Sao Paulo, Sao Paulo, Brazil. f.calo@usp.br FAU - Rodini, Camila Oliveira AU - Rodini CO FAU - Ramalho, Luciana Maria Pedreira AU - Ramalho LM FAU - Mantesso, Andrea AU - Mantesso A FAU - Nunes, Fabio Daumas AU - Nunes FD LA - eng PT - Journal Article DEP - 20090311 PL - Denmark TA - J Oral Pathol Med JT - Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology JID - 8911934 RN - 0 (Biomarkers, Tumor) RN - 0 (Proto-Oncogene Proteins) RN - 0 (WNT5A protein, human) RN - 0 (Wnt Proteins) RN - 0 (Wnt-5a Protein) RN - 0 (beta Catenin) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Biomarkers, Tumor MH - Carcinoma, Squamous Cell/*metabolism/pathology MH - Cell Membrane/metabolism MH - Cell Nucleus/metabolism MH - Cell Transformation, Neoplastic MH - Cheilitis/etiology/*metabolism MH - Cytoplasm/metabolism MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Immunoenzyme Techniques MH - Lip Neoplasms/*metabolism/pathology MH - Matrix Metalloproteinase 3/*biosynthesis MH - Mouth Mucosa/metabolism/pathology MH - Proto-Oncogene Proteins/*biosynthesis/physiology MH - Retrospective Studies MH - Signal Transduction MH - Sunlight/adverse effects MH - Wnt Proteins/*biosynthesis/physiology MH - Wnt-5a Protein MH - beta Catenin/*biosynthesis EDAT- 2009/05/29 09:00 MHDA- 2009/12/16 06:00 CRDT- 2009/05/29 09:00 PHST- 2009/05/29 09:00 [entrez] PHST- 2009/05/29 09:00 [pubmed] PHST- 2009/12/16 06:00 [medline] AID - JOP756 [pii] AID - 10.1111/j.1600-0714.2009.00756.x [doi] PST - ppublish SO - J Oral Pathol Med. 2009 Oct;38(9):708-15. doi: 10.1111/j.1600-0714.2009.00756.x. Epub 2009 Mar 11.