In-depth analysis of molecular alterations within normal and tumour tissue from an entire bronchial tree

Stephen K Sikkink, Triantafillos Liloglou, Paul Maloney, John R Gosney, John K Field

Research output: Contribution to journalArticle (journal)peer-review

24 Citations (Scopus)


Using laser capture microdissection (LCM), fluorescent microsatellite analysis and immunohistochemical analysis, we have constructed a detailed topographical molecular map of the entire bronchial tree surrounding a primary bronchial squamous carcinoma in order to establish the relationship between the molecular damage within the airway and that in the tumour itself. Allelic imbalance was analysed using markers on chromosomes 3, 9, 13 and 17. In addition, immunohistochemical analysis for p53 and cyclin D1 expression was performed. Analysis revealed allelic imbalance at several loci at the tumour site but also in 83% of the histologically normal airway specimens of the upper and lower lobes. The fractional allele loss (FAL) value was statistically higher (0.75+/-0.13) in the tumour site than in the distal site of the upper (0.42+/-0.09) and lower lobes (0.31+/-0.08). Immunohistochemical analysis revealed overexpression of p53 and cyclin D1 protein within histologically normal bronchial epithelium, thus confirming previous reports for their early involvement in lung tumour development. This is to date the largest in-depth study of allelic imbalance using LCM in a single individual. The patterns of allele-specific imbalance observed support a clonal or oligoclonal expansion model of outgrowths throughout the lung. The widespread incidence of genetic changes in the whole of lung most likely represents smoking-induced alterations and emphasize the complexity of the field cancerization concept. Our findings point to the need for in-depth studies of the whole bronchial tree tissue surrounding lung carcinomas, in order to identify the genetic changes that differentiate preneoplastic and neoplastic stages in lung carcinogenesis.

Original languageEnglish
Pages (from-to)589-95
Number of pages7
JournalInternational Journal of Oncology
Issue number3
Publication statusPublished - 1 Mar 2003


  • Aged
  • Alleles
  • Allelic Imbalance
  • Bronchi/chemistry
  • Bronchial Neoplasms/chemistry
  • Carcinoma, Non-Small-Cell Lung/chemistry
  • Carcinoma, Squamous Cell/chemistry
  • Cell Transformation, Neoplastic/genetics
  • Clone Cells/chemistry
  • Cyclin D1/biosynthesis
  • DNA, Neoplasm/genetics
  • Disease Progression
  • Epithelial Cells/chemistry
  • Gene Expression Regulation, Neoplastic
  • Genes, p53
  • Humans
  • Lasers
  • Lung/chemistry
  • Lung Neoplasms
  • Male
  • Microsatellite Repeats
  • Neoplasm Proteins/analysis
  • Neoplastic Stem Cells/chemistry
  • Proliferating Cell Nuclear Antigen/biosynthesis
  • Tumor Suppressor Protein p53/biosynthesis


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