Midkine expression in oral squamous cell carcinoma and leukoplakia

J Oral Pathol Med. 2012 Jan;41(1):21-6. doi: 10.1111/j.1600-0714.2011.01049.x. Epub 2011 May 20.

Abstract

Background: Midkine (MK), a 13-kDa heparin-binding growth factor, is overexpressed in various human cancers. However, its role in the development and progression of oral cavity squamous cell carcinoma (OCSCC) is still unclear. Thus, the aim of this study was to evaluate the expression of MK in samples of OCSCC, leukoplakia, and healthy oral mucosa (control).

Methods: Surgically excised specimens from patients with primary OCSCC (n = 28) were immunostained for MK, Ki-67, PCNA, p53, bcl-2, Bax, and CD31. Besides this, MK expression was also investigated in leukoplakia and normal oral mucosa. The relationship of MK(+) cells with clinical parameters (tumor location, tumor size, lymph node metastasis, and survival) and microscopic parameters (WHO histological grading, intensity of inflammation, proliferation index, apoptosis, and angiogenesis) was also evaluated.

Results: The results showed that MK expression was increased in OCSCC in relation to leukoplakia and normal mucosa. Furthermore, MK expression was increased in late-stage tumors (T3/T4) compared with early-stage lesions (T1/T2). MK-positive lesions also showed increased expression of the anti-apoptotic protein bcl-2.

Conclusion: OCSCC, particularly late-stage tumors, exhibits increased MK expression, which may be involved in tumor progression via upregulation of anti-apoptotic genes, as shown by the augmented bcl-2 positivity in MK-positive tumors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / secondary
  • Cell Proliferation
  • Cytokines / analysis*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Ki-67 Antigen / analysis
  • Leukoplakia, Oral / pathology*
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Midkine
  • Mouth Mucosa / pathology
  • Mouth Neoplasms / pathology*
  • Neoplasm Grading
  • Neoplasm Staging
  • Neovascularization, Pathologic / pathology
  • Nerve Growth Factors / analysis*
  • Platelet Endothelial Cell Adhesion Molecule-1 / analysis
  • Proliferating Cell Nuclear Antigen / analysis
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Retrospective Studies
  • Survival Rate
  • Tumor Suppressor Protein p53 / analysis
  • bcl-2-Associated X Protein / analysis

Substances

  • BAX protein, human
  • Cytokines
  • Ki-67 Antigen
  • Nerve Growth Factors
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Midkine