title: DNA ploidy and cell cycle protein expression in oral squamous cell carcinomas with and without lymph node metastases.
abstract: BACKGROUND
  Oral squamous cell carcinoma (OSCC) is the most frequently occurring malignant tumour in the oral cavity. OSCC arises because of multiple genetic alterations. Cell cycle aberrations and aneuploidy are reportedly among the main characteristics of cancer cells and are associated with aggressive growth and poor prognosis.
  
  
  METHODS
  The study sample included 47 non-metastasised and 39 metastasised primary OSCC, with matched positive cervical lymph nodes and 17 normal oral mucosa samples. Tissue microarrays (TMAs) were prepared with a minimum of three cores from each case. TMA sections were cut and immunostained with MCM2, Ki-67, geminin and cyclin D1 antibodies. DNA image analysis was performed on the whole tissue section before TMAs were created.
  
  
  RESULTS
  The results revealed that there were no differences in cell cycle protein expression in different areas of the tumours or between the metastatic and non-metastatic carcinomas. None of the cell cycle proteins showed significant differences between the lymph node metastasis and the primary OSCC, except for Ki-67. Geminin/Ki-67 ratio showed significant difference between metastatic and non-metastatic tumours. Aneuploidy was detected in all (100%) cases of OSCC. Similarly, all lymph node samples (39 cases) were aneuploid.
  
  
  CONCLUSIONS
  The results suggest that although there was dysregulation of cell cycle regulatory proteins, only Ki-67 and the MCM2/Ki-67 and geminin/Ki-67 ratios may have prognostic significance in oral cancer. DNA ploidy alone was not specific and may not be a good tool to evaluate prognosis or metastatic progression in oral cavity carcinomas.
authors.affiliation: Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, UK.
authors.forename: Ibtisam M
authors.identifier: http://orcid.org/0000-0002-8554-436X
authors.initials: IM
authors.lastname: Zargoun
authors.affiliation: Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, UK.
authors.forename: L
authors.initials: L
authors.lastname: Bingle
authors.affiliation: Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, UK.
authors.forename: P M
authors.initials: PM
authors.lastname: Speight
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism* / Q000556:secondary; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D011003:Ploidies
chemical_list: D018797:Cell Cycle Proteins
keywords: DNA ploidy; cell cycle proteins; image cytometry; oral squamous cell carcinoma