Prognostic significance of MCM7 expression in the bronchial brushings of patients with non-small cell lung cancer (NSCLC)

Lung Cancer. 2012 Jul;77(1):176-82. doi: 10.1016/j.lungcan.2012.03.001. Epub 2012 Mar 26.

Abstract

Purpose: To identify potential biomarkers for the prognosis of non-small cell lung cancer (NSCLC) patients by using bronchial brushing specimens.

Methods: The expression of MCM7, Ki67 and EGFR was evaluated in 494 NSCLC tissues and 174 bronchial brushings using immunohistochemical and immunocytochemical techniques. Associations between protein expression and clinico-pathologic parameters were assessed, and the impact on overall survival (OS) was analyzed.

Results: High expression of MCM7, Ki67 and EGFR was detected in 33.3%, 23.5% and 12.7% of tissues and in 52.4%, 52.7% and 20.6% of bronchial brushings, respectively. Expression of MCM7 and Ki67 was associated with squamous cell carcinoma (SCC) in both tissues and bronchial brushings (MCM7: P = 0.0007, 0.00003; Ki67: P < 0.00001, 0.00001). Overexpression of MCM7 in tumor tissues was detected more frequently in poorly differentiated tumors (P = 0.0120) and non-bronchioloalveolar carcinomas (non-BACs) (P = 0.0238). EGFR overexpression was observed in tissues of larger tumors (P = 0.00004) and in bronchial brushings at later stage (P = 0.0262). Kaplan-Meier curves indicated that patients with overexpression of MCM7 or Ki67 had a poorer OS compared to those with low expression for all stages (P < 0.00001, 0.0233) and early-stages (P < 0.00001, 0.0032). In particular, the patients with MCM7 overexpression in bronchial brushings had a poorer prognosis (P = 0.0045). Multivariate Cox regression analysis showed that MCM7 was an independent prognostic indicator both in tissue samples and bronchial brushings.

Conclusions: Our data suggest that MCM7 and Ki67 in tumor tissues may be potential markers of a poor prognosis for NSCLC patients. MCM7 in bronchial brushings also showed an independent prognostic value, which may be useful when biopsies are unavailable.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy
  • Bronchi / metabolism
  • Bronchi / pathology*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Cell Cycle Proteins / metabolism
  • DNA-Binding Proteins / metabolism
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / metabolism
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Minichromosome Maintenance Complex Component 7
  • Multivariate Analysis
  • Nuclear Proteins / metabolism
  • Prognosis
  • Proportional Hazards Models
  • Tissue Array Analysis

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Ki-67 Antigen
  • Nuclear Proteins
  • EGFR protein, human
  • ErbB Receptors
  • MCM7 protein, human
  • Minichromosome Maintenance Complex Component 7