title: Expression of Mcm2, geminin and Ki67 in normal oral mucosa, oral epithelial dysplasias and their corresponding squamous-cell carcinomas.
abstract: Proteins necessary for the normal regulation of the cell cycle include minichromosome maintenance protein 2 (Mcm2) and geminin. These are overexpressed in several premalignant and malignant tumours. The Mcm2/Ki67 ratio can be used to estimate the population of cells that are in early G(1) (licensed to proliferate), and the geminin/Ki67 ratio can determine the relative length of G(1). A high ratio indicates a short G(1) and a high rate of cell proliferation. Mcm2 and geminin have been scarcely explored in oral epithelial dysplasia (OED) and oral squamous-cell carcinoma (OSCC). The purpose of this study was to identify the expression pattern of Mcm2, Ki67 and geminin in normal oral mucosa (NOM), OED and their subsequent OSCC, to determine if expression could help predict the prognosis of OED. Paraffin sections of 41 OED cases that progressed to carcinoma, 40 OED without malignant progression, 38 OSCC and 15 NOM were immunostained with antibodies against Mcm2, geminin and Ki67. Labelling indices (LIs) increased progressively from NOM, OED and OSCC (Mcm2, P<0.001; geminin, P<0.001 and Ki67, P<0.001). In all the OED cases (n=81) the levels of expression of Mcm2 (LI, 73.6), geminin (LI, 24.4) and Ki67 (LI, 44.5) were elevated indicating a constant cell-cycle re-entry. When the OED groups were compared, Mcm2 protein expression was higher in the OED with malignant progression (P=0.04), likewise there was a significant increase in the Mcm2/Ki67 and geminin/Ki67 ratios (P=0.04 and 0.02 respectively). Mcm2 and geminin proteins seem to be novel biomarkers of growth and may be useful prognostic tools for OED.
authors.affiliation: Department of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, UK.
authors.forename: A
authors.initials: A
authors.lastname: Torres-Rendon
authors.forename: S
authors.initials: S
authors.lastname: Roy
authors.forename: G T
authors.initials: GT
authors.lastname: Craig
authors.forename: P M
authors.initials: PM
authors.lastname: Speight
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000737:chemistry*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000032:analysis*; D005260:Female; D064248:Geminin; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D064111:Minichromosome Maintenance Complex Component 2; D009061:Mouth Mucosa / Q000737:chemistry*; D009062:Mouth Neoplasms / Q000737:chemistry*; D009687:Nuclear Proteins / Q000032:analysis*; D011230:Precancerous Conditions / Q000737:chemistry*; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C577995:GMNN protein, human; D064248:Geminin; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2