Expression of Minichromosome Maintenance 2 (MCM2), Ki-67, and Cell-Cycle-Related Molecules, and Apoptosis in the Normal-Dysplasia-Carcinoma Sequence of the Oral Mucosa

Abstract

Objective: We examined cell cycle and cell death biomarker trends with the normal-dysplasia-carcinoma sequence of the oral epithelia analyzing the pathological significance of a new biomarker, minichromosome maintenance 2 (MCM2). Methods: This study analyzed 12 patients with normal oral epithelia, 69 with dysplasia, and 35 with squamous cell carcinoma (SCC); in 13 patients, SCCs were preceded by dysplasia. The sections were immunostained for MCM2, Ki-67, P53, P27^Kip1 and P21^CIP1/WAF1, and conducted by TUNEL methods. Western blot analysis of MCM2 was performed in the 4 human cultured oral SCCs, all of which showed the expression. Results: Significantly higher labeling indices (LI; %) of MCM2, Ki-67, and P53, as well as lower LI of TUNEL indices (TI; %), P27, and P21 were noted in the SCCs than in the dysplasias. The 13 dysplasias developed SCC with significantly higher LI of MCM2 and P53, and lower LI of P21 than the other dysplasias (each p < 0.05). The LI of MCM2, P21 and the TI were not correlated with P53 expression. Conclusions: Oral dysplasia was characterized by lower cell proliferation and a higher frequency of cell death compared to SCCs. The higher LI of MCM2 and P53 and the lower LI of P21 might predict malignant transformation of oral dysplasia. MCM2 is regulated via a P53-independent pathway, and a useful biomarker of proliferating cells.

Expression of Mcm2, geminin and Ki67 in normal oral mucosa, oral epithelial dysplasias and their corresponding squamous-cell carcinomas

“…The present study showed similar results to that of Kodani et al (2001), although the LIs for Mcm2 and Ki67 were higher in our study. The reason for this might be that Kodani et al quantified cells throughout the whole thickness of the epithelium, from basal to surface epithelial layers.…”

“…Although these results need to be confirmed by other similar studies, Ki67 and geminin showed no significant difference between the OED groups, however Mcm2 had a marginally but significantly higher mean LI, in the OED that progressed to OSCC than the OED with no history of malignant progression, this was also observed previously (Kodani et al, 2001). These findings could suggest that cells in OED with malignant progression have an increased number of cells licensed to proliferate.…”

“…This suggests that the epithelial basal and suprabasal compartments in NOM have a low and controlled proliferation rate but with a continuous proliferative capacity. Low LIs in normal tissues have also been observed by other authors for Mcm2 and Ki67 in oral mucosa (Kodani et al, 2001), larynx and prostate tissues (Meng et al, 2001), and for geminin in breast tissue (Shetty et al, 2005).…”

“…Ki67 Geminin In the oral mucosa only a few studies have explored this (Kodani et al, 2001(Kodani et al, , 2003Scott et al, 2006). To the best of our knowledge, this is the first study in which geminin or Mcm2/Ki67 and geminin/Ki67 ratios have been evaluated in NOM or in oral dysplasias and carcinomas.…”

MCM3 as a Novel Diagnostic Marker in Benign and Malignant Salivary Gland Tumors

“…In another study in 2008, Vargas et (Vargas et al, 2008). Studies that have been carried out regarding the cancer of bladder, prostate, breast and oral squamous cell carcinoma have also confirmed the higher expression of MCM2 than Ki-67 (Kodani et al, 2001;Meng et al, 2001;Gonzalez et al, 2003;Korkolopoulou et al, 2005). Szelachowska et al (2006) demonstrated that MCM2 protein predicts better prognosis than Ki-67 in oral cavity squamous cell carcinoma (Szelachowska et al, 2006).…”