Distinct claudin expression profile in histologic subtypes of lung cancer

Lung Cancer. 2007 Aug;57(2):159-67. doi: 10.1016/j.lungcan.2007.02.018. Epub 2007 Apr 6.

Abstract

Purpose: Claudins are the main constituents of tight junctions. Little is known about their expression and localization in the normal bronchial epithelium and in lung cancer.

Patients and methods: One hundred four lung cancer tissue blocks were studied including 46 adenocarcinomas (ADC), 30 squamous cell carcinomas (SCC), 15 small cell lung cancers (SCLC), 8 typical and 5 atypical carcinoids. All slides contained normal bronchial mucosa as well. Immunohistochemistry using antibodies against claudins-1, -2, -3, -4, and -7 proteins, as well as semi-quantitative estimation were performed. RT-PCR analysis was also carried out in 22 immunohistochemically representative tumor samples.

Results: Normal bronchial epithelial cells expressed all the examined claudin proteins. When compared, SCLCs and carcinoids showed striking differences in regard to claudins-1, -3, and -4 expressions (p<0.0001, p<0.0001, and p<0.0004, respectively), whereas ADCs and SCCs revealed significant differences in claudins-3, -4, and -7 expressions (p<0.0001, p<0.0001, and p<0.0053, respectively). However, comparison of ADCs with SCLCs revealed significant difference only in claudin-2 expression (p<0.0002). The comparison of ADCs and carcinoids resulted in significant differences regarding claudins-1, -3, and -4 expressions (p<0.0006, p<0.0001, and p<0.0001, respectively). SCCs and SCLCs varied in respect to claudin-2, -3, and -4 expressions (p<0.0009, p<0.0001, and p<0.0019, respectively), whereas SCCs and carcinoids showed different claudins-1 and -4 expressions (p<0.0076 and p<0.0045, respectively). RT-PCR analysis revealed parallel changes in the mRNA and protein expression of certain claudins.

Conclusions: The observed distinct claudin expression profile within the non-small cell lung cancer group, further, the marked differences between SCLCs and carcinoids may have differential diagnostic impact, and the overexpression of certain claudins might have therapeutic implications.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Bronchi / metabolism
  • Carcinoid Tumor / genetics
  • Carcinoid Tumor / metabolism
  • Carcinoma, Small Cell / genetics
  • Carcinoma, Small Cell / metabolism
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Claudin-1
  • Claudin-3
  • Claudin-4
  • Claudins
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / classification
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Respiratory Mucosa / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • CLDN1 protein, human
  • CLDN2 protein, human
  • CLDN3 protein, human
  • CLDN4 protein, human
  • CLDN7 protein, human
  • Claudin-1
  • Claudin-3
  • Claudin-4
  • Claudins
  • Membrane Proteins
  • RNA, Messenger