Minichromosome Maintenance Complex (MCM) Genes Profiling and MCM2 Protein Expression in Cervical Cancer Development

Abstract

Objective: Minichromosome maintenance complex (MCM) proteins are essential for the process of DNA replication<br /> and cell division. This study aimed to evaluate MCM genes expression profiles and MCM2 protein in HPV-associated<br /> cervical carcinogenesis. Methodology: MCM2, 4, 5 and 7 genes expression profiles were evaluated in three cervical<br /> tissue samples each of normal cervix, human papillomavirus (HPV)-infected low grade squamous intraepithelial<br /> lesion (LSIL), high grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC), using Human<br /> Transcriptome Array 2.0 and validated by nCounter® PanCancer Pathway NanoString Array. Immunohistochemical<br /> expression of MCM2 protein was semi-quantitatively assessed by histoscore in tissue microarrays containing 9 cases of<br /> normal cervix, 10 LSIL, 10 HSIL and 42 cases of SCC. Results: MCM2, 4, 5 and 7 genes expressions were upregulated<br /> with increasing fold change during the progression from LSIL to HSIL and the highest in SCC. MCM2 gene had the<br /> highest fold change in SCC compared to normal cervix. Immunohistochemically, MCM2 protein was localised in<br /> the nuclei of basal cells of normal cervical epithelium and dysplastic-neoplastic cells of CIN and SCC. There was a<br /> significant difference in MCM2 protein expression between the histological groups (P = 0.039), and histoscore was the<br /> highest in HSIL compared to normal cervix (P = 0.010). Conclusion: The upregulation of MCM genes expressions in<br /> cervical carcinogenesis reaffirms MCM as a proliferative marker in DNA replication pathway, whereby proliferation of<br /> dysplastic and cancer cells become increasingly dysregulated and uncontrolled. A strong expression of MCM2 protein<br /> in HSIL may aid as a concatenated screening tool in detecting pre-cancerous cervical lesions.