Overexpression of BMP-2/4, -5 and BMPR-IA associated with malignancy of oral epithelium

Oral Oncol. 2001 Apr;37(3):225-33. doi: 10.1016/s1368-8375(00)00087-7.


The aim of the present study was to determine the relationships between bone morphogenetic proteins (BMPs), BMP receptor type IA and carcinogenesis of oral epithelium. A retrospective study was performed on material obtained from oral mucosa, including nine cases of normal mucosa (NB), eight cases of nonspecific chronic inflammation (NCI), seven cases of hyperkeratosis (HK), five cases of squamous cell papilloma (SCP), 29 cases of squamous cell carcinoma (SCC) with various grades of differentiation and 10 cases of epithelium adjacent to carcinoma (EAC). Six cases of NB from hard palate (NHP) were chosen as a control group. The benign groups consisted of NCI, HK and SCP. The antibodies against BMP-2/4, -5, receptor BMPR-IA and purified bovine BMP (bBMP-McAb) were utilised using an immunocytochemical method. The results demonstrated that the immunostaining of BMP-2/4, BMP-5, BMPR-IA and bBMP-McAb was weak and not consistent in normal and benign groups. The immunoreactivity level was independent of the clinical and pathological grading of SCC. All cases of SCC showed positive staining for BMP-2/4, BMP-5, BMPR-IA and bBMP-McAb except for three cases and one case of SCC which negatively stained for BMP-2/4 and BMP-5, respectively. The staining intensity and proportion of the positively stained cells were markedly increased in SCC when compared with that of the normal and benign groups except for EAC. The metastatic carcinoma cells in lymph nodes were strongly and positively stained for BMP-2/4 and BMP-5 when compared with the primary lesions. Our results indicate that there was an overexpression of BMP-2/4, BMP-5, bBMP-McAb and BMPR-IA in the high-risk premalignant and malignant lesions of oral epithelium. Our findings suggest that BMP-2/4 and BMP-5 but not BMPR-IA might be involved in the metastasis of oral carcinoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 5
  • Bone Morphogenetic Protein Receptors, Type I
  • Bone Morphogenetic Proteins / analysis*
  • Carcinoma, Squamous Cell / metabolism*
  • Case-Control Studies
  • Cell Membrane / chemistry
  • Cytoplasm / chemistry
  • Epithelium / chemistry
  • Humans
  • Immunohistochemistry
  • Leukoplakia, Oral / genetics
  • Lymphatic Metastasis
  • Mouth Mucosa / chemistry
  • Mouth Neoplasms / metabolism*
  • Neoplasm Proteins / analysis*
  • Palate
  • Papilloma / genetics
  • Precancerous Conditions / metabolism*
  • Protein-Serine-Threonine Kinases / analysis*
  • Receptors, Growth Factor / analysis*
  • Retrospective Studies
  • Statistics, Nonparametric
  • Transforming Growth Factor beta*


  • BMP2 protein, human
  • BMP5 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 5
  • Bone Morphogenetic Proteins
  • Neoplasm Proteins
  • Receptors, Growth Factor
  • Transforming Growth Factor beta
  • Protein-Serine-Threonine Kinases
  • BMPR1A protein, human
  • Bone Morphogenetic Protein Receptors, Type I