Protein overexpression and gene amplification of cellular mesenchymal-epithelial transition factor is associated with poor prognosis in micropapillary-predominant subtype pulmonary adenocarcinoma

Hum Pathol. 2018 Feb:72:59-65. doi: 10.1016/j.humpath.2017.10.031. Epub 2017 Nov 9.

Abstract

Micropapillary-predominant subtype pulmonary adenocarcinoma (MPPAC) is a subtype of lung cancer with poor prognosis. Cellular mesenchymal-epithelial transition factor (c-MET) is a promising pharmaceutic target found to be associated with the survival of patients with pulmonary adenocarcinoma. In this study, we aimed to analyze c-MET protein overexpression and gene amplification in MPPAC samples and to elucidate their relationship with the clinicopathological characteristics of the patients. c-MET protein expression was examined by immunohistochemical analyses, and gene amplification was detected by fluorescence in situ hybridization. A total of 86 MPPAC cases were included in this study. The prevalence of c-MET protein overexpression and gene amplification were 62.8% and 10.5%, respectively. C-MET protein overexpression was significantly associated with smoking status, lymphatic and venous invasion, and tumor-node-metastasis stage (P = .014, P = .040, and P = .004, respectively), but c-MET gene amplification showed no relation with any of these characteristics. Univariate analysis revealed that pleural invasion, lymph node metastasis, lymphatic and venous invasion, tumor-node-metastasis stage, c-MET protein overexpression, and c-MET gene amplification were associated with poor prognosis (P = .041, P < .001, P = .001, P < .001, P = .001 and P = .001, respectively), but only c-MET gene amplification was an independent prognostic marker (P = .04). These results indicated that c-MET is an important biomarker. Also, c-MET protein overexpression and gene amplification are highly related to poor prognosis in patients with MPPAC.

Keywords: Cellular mesenchymal-epithelial transition factor; Gene amplification; Micropapillary; Prognosis; Pulmonary adenocarcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Female
  • Gene Amplification / genetics
  • Humans
  • In Situ Hybridization, Fluorescence / methods
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / pathology*
  • Lymphatic Metastasis / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging / methods
  • Prognosis
  • Proto-Oncogene Proteins c-met / metabolism*

Substances

  • Biomarkers, Tumor
  • MET protein, human
  • Proto-Oncogene Proteins c-met