MCM4 and MCM7, potential novel proliferation markers, significantly correlated with Ki-67, Bmi1, and cyclin E expression in esophageal adenocarcinoma, squamous cell carcinoma, and precancerous lesions

Hum Pathol. 2016 Nov:57:126-135. doi: 10.1016/j.humpath.2016.07.013. Epub 2016 Jul 29.

Abstract

Minichromosomal maintenance (MCM) proteins are participants of DNA replication and may represent more accurate markers in determining the proliferative fraction within a tumor than proliferative marker Ki-67. Our study investigated the correlation between MCM4 and MCM7 expression and Ki-67, Bmi1, and cyclin E expression in esophageal adenocarcinoma, squamous cell carcinoma, and precancerous lesions. MCM4 and MCM7 expression had similar distribution as Ki-67 and Bmi1 expression in esophageal carcinoma and precancerous lesions. The mean percentage of MCM4, MCM7, and Ki-67 expression increased from squamous epithelium (5.5%, 7.3%, and 5.9%, respectively), to columnar cell metaplasia (11.2, 13.5%, and 3.4%), Barrett's esophagus (27.7%, 35.3%, and 8.3%), low-grade dysplasia (42.6%, 52.2%, and 12.9%), high-grade dysplasia (63.2%, 77.7%, and 29.6%), adenocarcinoma (61.3%, 75.5%, and 24.5%), and squamous cell carcinoma (74.1, 85.4%, and 36.3%). The percentages of MCM4 and MCM7 expression were significantly higher than Ki-67 expression. Using univariate analysis we found a high percentage of MCM4 expression (>70%) to be significantly associated with lymph node metastasis and shorter survival in the adenocarcinoma group. We also demonstrated the percentage of MCM4 and MCM7 expression to be significantly correlated with Ki-67, Bmi1, and cyclin E expression in esophageal carcinoma and precancerous lesions. MCM4 and MCM7 may serve as more sensitive proliferative markers for the evaluation of esophageal lesions.

Keywords: Barrett's esophagus; Esophageal adenocarcinoma; Esophageal squamous cell carcinoma; Ki-67; MCM4; MCM7.

MeSH terms

  • Adenocarcinoma / chemistry*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Barrett Esophagus / metabolism*
  • Barrett Esophagus / mortality
  • Barrett Esophagus / pathology
  • Carcinoma, Squamous Cell / chemistry*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Cell Proliferation*
  • Chi-Square Distribution
  • Cyclin E / analysis*
  • Esophageal Neoplasms / chemistry*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / analysis*
  • Lymphatic Metastasis
  • Male
  • Minichromosome Maintenance Complex Component 4 / analysis*
  • Minichromosome Maintenance Complex Component 7 / analysis*
  • Multivariate Analysis
  • Neoplasm Grading
  • Polycomb Repressive Complex 1 / analysis*
  • Precancerous Conditions / chemistry*
  • Precancerous Conditions / mortality
  • Precancerous Conditions / pathology
  • Predictive Value of Tests
  • Reproducibility of Results
  • Risk Factors
  • Tissue Array Analysis

Substances

  • BMI1 protein, human
  • Cyclin E
  • Ki-67 Antigen
  • Polycomb Repressive Complex 1
  • MCM4 protein, human
  • MCM7 protein, human
  • Minichromosome Maintenance Complex Component 4
  • Minichromosome Maintenance Complex Component 7

Supplementary concepts

  • Adenocarcinoma Of Esophagus