Correlation between levels of expression of minichromosome maintenance proteins, Ki-67 proliferation antigen and metallothionein I/II in laryngeal squamous cell cancer

Abstract

MCM2, MCM3 and MCM7 are minichromosome maintenance proteins found in dividing cells and they play a role in DNA synthesis. Increased MCM expression level is observed in cells of different cancer types. Additionally, metallothioneins (MT-I/II) are involved in control of cell proliferation and differentiation and changes of their expression are observed in many types of cancer. Ki-67 is known cancer cell proliferation antigen currently used in prognostic evaluation. The study material consisted of 83 laryngeal squamous cell cancer (LSCC) cases and 10 benign hypertrophic lesions of larynx epithelium as a control group. For the present study, laryngeal cancer cell line HEp-2 and human keratinocytes were employed, and to evaluate expression of all the markers, immunohistochemical method (IHC), immunofluorescence (IF) and western blot analysis were used. Statistical analysis showed strong positive correlation between expression of MCM2, MCM3, MCM7 and Ki-67 antigen in LSCC. Additionally, moderate positive correlation was observed between MCM3 and MT-I/II expression. In cancer cells, the level of expression of MCM3, MCM2, MCM7 and Ki-67 markers was increasing with the grade of LSCC malignancy. IF and western blot analysis showed higher MCM2, MCM3, MCM7 expression in HEp-2 cells in comparison to their expression in keratinocytes. MCM proteins might be useful markers of cell proliferation in LSCC.

MCM5 Expression Is Associated With the Grade of Malignancy and Ki-67 Antigen in LSCC

“…The grade of malignancy (G) and the clinical stage of LSCC were based on the TNM classification determined by the International Union Against Cancer (UICC). The clinical characteristics of the patient group are summarised in Table I and have been presented previously (8).…”

“…It is a non-histone protein present in the nucleus of dividing cells (20). In LSCC, the increase in the Ki-67 proliferation index is associated with progression and greater tumour aggressiveness (8,21,22). To the best of our knowledge, this is the first study examining the relationship of Metallothionein I and II (MT-I/II) with MCM5 in LSCC.…”

“…Expression of MCM2-7 is detected in the nucleus only in dividing cells. However, it is not observed in the interphase during differentiation or in ageing cells (8).…”

“…It is also believed that MT-I/II are involved in the control of cell proliferation and differentiation (24). MT-I/II showed a mean positive correlation with MCM3 protein in LSCC (8).…”

“…So far, the expression of MCM proteins and their association with clinicopathological data in laryngeal cancer have been poorly understood. However, increased expression of MCM2 has been observed in LSCC (8,18,19).…”