Gain of 1q25-32, 12q23-24.3, and 17q12-22 Facilitates Tumorigenesis and Progression of Human Squamous Cell Lung Cancer

J Pathol. 2006 Oct;210(2):205-13. doi: 10.1002/path.2050.

Abstract

To explore the genetic changes involved in the stepwise development of lung cancer, we have determined the genetic events associated with the histological progression from normal bronchial epithelium to squamous cell carcinoma. Comparative genomic hybridization was used to identify chromosomal imbalances in 54 microdissected samples, including squamous metaplasia, dysplasia, carcinoma in situ, and invasive tumour derived from 23 patients with squamous cell carcinoma of the lung. Histopathological progression was accompanied by an increased number of chromosomal abnormalities. Gains of 1q25-32, 12q23-24.3, and 17q12-22, in particular, were detected at high frequencies in both carcinoma in situ and invasive tumours and were found more often in the cases with lymph node metastases than in those without. Our previous expression profiling of squamous cell carcinomas had identified overexpression of laminin5 gamma2, a gene located at 1q25-31. Therefore, this was investigated at the protein level by immunohistochemical analysis in 336 samples of squamous cell carcinoma of the lung. Consistent with the genomic data for this region, the expression level of laminin5 gamma2 was higher in the primary tumours with lymph node metastases than in tumours without metastases (p = 0.012). These data suggest that gains of genes from 1q25-32, 12q23-24.3, and 17q12-22 facilitate tumorigenesis and progression of squamous cell carcinoma of the lung, and may serve as potential predictors for this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / secondary
  • Cell Transformation, Neoplastic / genetics*
  • Chromosome Aberrations*
  • Chromosomes, Human, Pair 1 / genetics
  • Chromosomes, Human, Pair 12 / genetics
  • Chromosomes, Human, Pair 17 / genetics
  • Disease Progression
  • Female
  • Humans
  • Laminin / metabolism
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lymphatic Metastasis
  • Male
  • Microdissection / methods
  • Middle Aged
  • Neoplasm Proteins / metabolism
  • Neoplasm Staging
  • Nucleic Acid Hybridization
  • Precancerous Conditions / genetics

Substances

  • LAMC2 protein, human
  • Laminin
  • Neoplasm Proteins