3q26 Amplification and polysomy of chromosome 3 in squamous cell lesions of the lung: a fluorescence in situ hybridization study.
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.
Pelosi
Giuseppe
G
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
Del Curto
Barbara
B
Trubia
Maurizio
M
Nicholson
Andrew G
AG
Manzotti
Michela
M
Veronesi
Giulia
G
Spaggiari
Lorenzo
L
Maisonneuve
Patrick
P
Pasini
Felice
F
Terzi
Alberto
A
Iannucci
Antonio
A
Viale
Giuseppe
G
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
D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C060615:SKIL protein, human; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase