Bone morphogenetic protein 6 expression in oral cavity squamous cell cancer is associated with bone invasion

Laryngoscope. 2013 Dec;123(12):3061-5. doi: 10.1002/lary.24267. Epub 2013 Jul 1.


Objectives/hypothesis: To evaluate bone invasion, survival, and expression of bone morphogenetic protein-6 (BMP-6) in oral cavity cancer in the context of known biomarkers indicative of poor prognosis.

Study design: Molecular expression study combined with retrospective chart review of corresponding patients at a tertiary care center.

Methods: Between 2000 and 2009, a total of 197 patients underwent resection for oral cavity squamous cell carcinoma. Of these, 30 pathologic specimens were chosen for further molecular analysis. These 30 patients were separated into three groups (10 per group) based on American Joint Committee on Cancer (AJCC) staging and staging based on size alone (TAJCC /SIZE ). The first group consisted of tumors staged as T2 /2 based on size less than 4 cm and that had no evidence of bone invasion. The T2 /4 group consisted of tumors that were upstaged from T2 based on bone invasion. The T4 /4 group consisted of tumors that were large with and without bone invasion. The expression of extracellular matrix metalloproteinase inducer (EMMPRIN), BMP-6, and epidermal growth factor receptor (EGFR) was examined using immunohistochemistry techniques. Patient demographics, tumor characteristics, survival, and recurrence were compared.

Results: Average follow-up was 21 months. Expression of BMP-6 was significantly higher in the T2 /4 cohort (tumor less than 4 cm with bony invasion) than the larger tumors without bone invasion (T4 /4 cohort, P = .05). In addition, increased BMP-6 expression correlated with aggressive behavior in the smaller tumors. Furthermore, increased EGFR expression positively correlated with increased levels of BMP-6.

Conclusions: Increased expression of BMP-6 in oral cavity cancer may affect bone invasion.

Keywords: Head and neck; bone morphogenetic protein-6; immunohistochemistry; oral cavity cancer; squamous cell carcinoma; tumor biomarkers.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / biosynthesis
  • Bone Morphogenetic Protein 6 / biosynthesis*
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Carcinoma, Squamous Cell / pathology
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mouth Mucosa / metabolism*
  • Mouth Mucosa / pathology
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Neoplasm Invasiveness*
  • Neoplasm Staging
  • Prognosis
  • Retrospective Studies


  • Biomarkers, Tumor
  • Bone Morphogenetic Protein 6