title: 3q26 Amplification and polysomy of chromosome 3 in squamous cell lesions of the lung: a fluorescence in situ hybridization study.
abstract: OBJECTIVE
  An overlapping area of gain at 3q26 has been reported in lung squamous cell carcinoma (SCC), but whether this also occurs in preneoplastic/preinvasive squamous cell proliferations and early-stage invasive carcinomas of the lung is still unknown.
  
  
  METHODS
  We evaluated the prevalence and the clinicopathologic implications of 3q26 amplification and polysomy of chromosome 3 in 31 preneoplastic/preinvasive squamous cell lesions of the bronchial mucosa and in 139 early-stage invasive pulmonary SCC, both of limited growth within the bronchial wall [early hilar SCC (EHSCC)] and involving the pulmonary parenchyma [parenchyma-infiltrating SCC (PISCC)]. Moreover, mRNA expression of two candidate genes (h-TERC and SKI-like), both mapping to the minimal common amplification region, was also studied by quantitative real-time reverse transcription-PCR.
  
  
  RESULTS
  3q26 amplification and polysomy of chromosome 3 were confined to malignant samples, with 37% of invasive SCC, and 27% of severe dysplasias/in situ carcinomas showing these chromosomal abnormalities. Amplification (with minimal common amplification region at 3q26.2), polysomy 3, concurrent amplification and polysomy 3, or other changes (monosomy) were found in 25 SCC and 1 dysplasia, 24 and 2, 2 and 0, and 1 and 0, respectively. Amplification was significantly associated with EHSCC, polysomy 3 with PISCC. 3q26 amplification correlated with increased tumor diameter and a history of smoking, whereas polysomy 3 correlated with tumor diameter, pT class, and p53, p21, and fascin immunoreactivity. No relationship of either 3q26 gain or polysomy was found with patients' survival. Overexpression of h-TERC or SKI-like mRNA was found in 3q26-amplified or polysomic SCC, with higher levels of h-TERC in the former and of SKI-like in the latter.
  
  
  CONCLUSIONS
  3q26 amplification and chromosome 3 polysomy may be related to the development of invasive SCC, with differential distribution in tumor subsets, despite substantial histologic uniformity. Both h-TERC and SKI-like may be involved in tumor progression.
authors.affiliation: Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan School of Medicine and Cancer Genetic Unit, IFOM Foundation-FIRC Institute of Molecular Oncology Foundation, Milan, Italy. giuseppe.pelosi@ieo.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pelosi
authors.forename: Barbara
authors.initials: B
authors.lastname: Del Curto
authors.forename: Maurizio
authors.initials: M
authors.lastname: Trubia
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Nicholson
authors.forename: Michela
authors.initials: M
authors.lastname: Manzotti
authors.forename: Giulia
authors.initials: G
authors.lastname: Veronesi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Spaggiari
authors.forename: Patrick
authors.initials: P
authors.lastname: Maisonneuve
authors.forename: Felice
authors.initials: F
authors.lastname: Pasini
authors.forename: Alberto
authors.initials: A
authors.lastname: Terzi
authors.forename: Antonio
authors.initials: A
authors.lastname: Iannucci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D012313:RNA / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000096:biosynthesis
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C060615:SKIL protein, human; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase