title: LAMC2 is a predictive marker for the malignant progression of leukoplakia.
abstract: BACKGROUND
  LAMC2 plays an important role in cancer invasion. The aim of this study was to (i) compare the immunoexpression of LAMC2 in different stages of oral squamous cell carcinoma (OSCC), early and advanced, and (ii) to evaluate LAMC2 as a marker of malignant transformation in leukoplakia.
  
  
  METHODS
  The expression of LAMC2 was examined by immunohistochemistry in 50 surgical specimens of advanced OSCC assembled as tissue microarrays, and by cDNA microarray in 43 surgical specimens of advanced OSCC. LAMC2 expression was further examined in 39 surgical specimens of early OSCC and in 93 incisional biopsy specimens of leukoplakia of the tongue, which exhibited epithelial dysplasia. The relationship of LAMC2 expression score with clinico-pathological characteristics was analyzed.
  
  
  RESULTS
  LAMC2 was remarkably upregulated in OSCC at the cancer-stroma interface. The grade of LAMC2 expression was significantly associated with the pattern and depth of invasion of OSCC. Foci of LAMC2-positive cells were observed in some cases of leukoplakia. The number and size of LAMC2-positive foci were significantly associated with the grade of dysplasia. The presence of LAMC2-positive foci was a significant predictive factor for the malignant progression of leukoplakia. LAMC2-positive leukoplakia had an approximately 11-fold increased risk of malignancy compared with LAMC2-negative leukoplakia.
  
  
  CONCLUSIONS
  The results of this study highlight the value of LAMC2 as a marker of cancer invasion. LAMC2-positive foci in leukoplakia suggest an imminent risk of cancer. LAMC2 immunostaining is expected to contribute to a more precise assessment of the malignancy of leukoplakia.
authors.affiliation: Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Chi Thi Kim
authors.initials: CT
authors.lastname: Nguyen
authors.affiliation: Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kei-Ichi
authors.initials: KI
authors.lastname: Morita
authors.affiliation: Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Department of Oral Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Harada
authors.affiliation: Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Miki
authors.affiliation: Department of Diagnostic Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Izumo
authors.affiliation: Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kou
authors.initials: K
authors.lastname: Kayamori
authors.affiliation: Oral Health Science Center, Tokyo Dental College, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yamaguchi
authors.affiliation: Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Sakamoto
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D007972:Leukoplakia, Oral / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D016016:Proportional Hazards Models; D012313:RNA / Q000378:metabolism; D014062:Tongue Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C400567:LAMC2 protein, human; D007797:Laminin; D012313:RNA
keywords: LAMC2; dysplasia; laminin; laminin-332; leukoplakia; oral squamous cell carcinoma