title: 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.
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.
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Choy
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642.
authors.forename: Amy
authors.initials: A
authors.lastname: LaLonde
authors.affiliation: Center for Human Development & Division of Digestive and Liver Diseases, Columbia University Medical Center, NY 10032.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Que
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642.
authors.forename: Tongtong
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester, Rochester, NY 14642. Electronic address: David_Zhou@urmc.rochester.edu.
authors.forename: Zhongren
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D001471:Barrett Esophagus / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D019927:Cyclin E / Q000032:analysis*; D004938:Esophageal Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis*; D008207:Lymphatic Metastasis; D008297:Male; D064148:Minichromosome Maintenance Complex Component 4 / Q000032:analysis*; D064168:Minichromosome Maintenance Complex Component 7 / Q000032:analysis*; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D063150:Polycomb Repressive Complex 1 / Q000032:analysis*; D011230:Precancerous Conditions / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012307:Risk Factors; D046888:Tissue Array Analysis
chemical_list: C069077:BMI1 protein, human; D019927:Cyclin E; D019394:Ki-67 Antigen; D063150:Polycomb Repressive Complex 1; C099243:MCM4 protein, human; C101624:MCM7 protein, human; D064148:Minichromosome Maintenance Complex Component 4; D064168:Minichromosome Maintenance Complex Component 7
keywords: Barrett's esophagus; Esophageal adenocarcinoma; Esophageal squamous cell carcinoma; Ki-67; MCM4; MCM7