Immunoexpression of Ki-67, MCM2, and MCM3 in Ameloblastoma and Ameloblastic Carcinoma and Their Correlations with Clinical and Histopathological Patterns

Abstract

Cell proliferation assays are performed using antibodies against nuclear proteins associated with DNA replication. These nuclear proteins have gained special interest to predict the biological and clinical behaviors of various tumors. The aim of this study was to analyze the presence of Ki-67 protein and the minichromosome maintenance-2 (MCM2) and maintenance-3 (MCM3) proteins in ameloblastoma. Materials and Methods. Cell proliferation marker expression levels were assessed via immunohistochemistry in 111 ameloblastoma cases (72 unicystic ameloblastoma samples, 38 solid/multicystic ameloblastoma samples, and 1 ameloblastic carcinoma). The label index was performed as described previously. Results. MCM2 and MCM3 showed higher proliferation indexes in all variants of ameloblastoma compared to the classic marker Ki-67. No correlation between the proliferation index and the clinical and protein expression data was observed. Conclusion. The results suggest that clinical features do not directly affect tumor cell proliferation. Moreover, the high levels of cellular proliferation of MCM2 and MCM3 compared with Ki-67 may indicate that MCM2 and MCM3 are more sensitive markers for predicting the growth rate and eventually might be helpful as a tool for predicting aggressive and recurrent behaviors in these tumors.

Comparison between Manual and Automated Methods for Ki-67 Immunoexpression Quantification in Ameloblastomas

“…Although highly reproducible, these cell counting methods are time-consuming, tedious, and exhausting. The modified version of the labeling index method with ImageJ [8] (DM scoring) enables the rater to mark the counted cells, thereby ensuring increased reproducibility and decreased fatigue during counting; however, this is still a manual method. Our present findings show that the manual methods used to determine the labeling index are reproducible, and the results correlate with the proliferation capacity of tumor cells in AM [6, 9, 13–16].…”

“…The manual scoring and DM scoring methods for Ki-67 immunostaining were performed according to Bologna-Molina et al [7] and Carreón-Burciaga et al [8], respectively.…”

“…DM scoring was completed as described by Carreón-Burciaga et al [8], and the Grid and Cell Counter plugins for ImageJ were used (https://imagej.nih.gov/ij/) (Figure 2). …”

“…However, this method does not enable the rater to mark the counted cells. In 2015 [8], a variation of this cell counting method using the ImageJ software was proposed. This software increased cell counting accuracy and enabled the marking of counted cells, thus improving the comparison between datasets.…”

Comparison between immunohistochemical expression of Ki-67 and MCM-3 in major salivary gland epithelial tumors in children and adolescents. Preliminary study

“…An evaluation of MCM protein expression levels may also provide an insight into the prognosis of neoplasms, as the proteins are inversely associated with tumor cell differentiation and their levels could be used as indicators of proliferation [8].…”