J Gynecol Oncol.  2012 Jan;23(1):11-15. 10.3802/jgo.2012.23.1.11.

Minichromosome maintenance 7 protein is a reliable biological marker for human cervical progressive disease

Affiliations
  • 1Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil. arvago@icb.ufmg.br
  • 2Department of Clinical and Toxicological Analysis, School of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil.
  • 3Department of Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
  • 4Department of Preventive Veterinary Medicine, School of Veterinary Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil.
  • 5Department of Medical Sciences, Federal University of Ouro Preto, Ouro Preto, Brazil.

Abstract


OBJECTIVE
This study focused on comparing the expression levels of p16, Ki-67, and minichromosome maintenance 7 (MCM7) protein in normal and affected cervical epithelium to ascertain the biological significance of these markers in detecting progressive cervical disease.
METHODS
A quantitative and based on-scanning-microscopy analysis of the three markers expression was performed in normal and cervical intraepithelial neoplasia (CIN) I, II, and III tissues. p16 area as well as p16, Ki-67, and MCM7 positive cells or nuclei were evaluated according to their distribution and extent through the cervical epithelium.
RESULTS
A clear p16 over-expression was observed in all the dysplastic epithelium tissue samples. The quantitative analysis of p16 area as well as the number of p16 positive cells was able to better discriminate the CIN lesions grades than the usual semi-quantitative analysis. The average Ki-67 labeling indexes for the normal epithelium, CIN I, CIN II, and CIN III groups were 19.8%, 27.3%, 32.8%, and 37.1%, respectively, whereas the mean MCM7 labeling indexes for the correspondent grades were 27.0%, 30.4%, 50.5%, and 67.2%. The Ki-67 and MCM7 labeling indexes were closely correlated with the CIN histological grade, with higher labeling indexe values obtained from the more severe lesions (p<0.05), being the MCM7 labeling indexes the highest values in all the CIN categories (p<0.05).
CONCLUSION
We observed a good correlation among the p16, Ki-67, and MCM7 data. In addition, MCM7 demonstrated to be a more efficient and sensitive marker to assess disease progression in the uterine cervix.

Keyword

Cervical intraepithelial neoplasia; Genes p16; Immuno-fluorescence analysis; Ki-67 antigen; MCM7 protein

MeSH Terms

Biomarkers
Cervical Intraepithelial Neoplasia
Cervix Uteri
Disease Progression
Epithelium
Female
Humans
Ki-67 Antigen
Ki-67 Antigen

Figure

  • Fig. 1 Comparative immuno-fluorescent analysis of Ki-67, p16, and minichromosome maintenance 7 (MCM7) markers expression in human-cervical tissue-samples obtained by loop electrosurgical excision procedure (LEEP). The diagnoses were independently reviewed/confirmed by three certified pathologists. Positive Ki-67 and MCM7 cells show fluorescence-labeling confined to the nucleus (white), whereas p16-positive cells show nuclear/and/cytoplasmic labeling (green). Nuclei were immuno-labeled with propidium-iodide (red). CIN, cervical intraepithelial neoplasia.


Reference

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