Paxillin expression and amplification in early lung lesions of high-risk patients, lung adenocarcinoma and metastatic disease.
BACKGROUND
Paxillin is a modular protein that localises to cell adhesion sites where it facilitates bidirectional communication between the intracellular actin cytoskeleton and the extracellular matrix. These complex and dynamic interactions are essential for cell adhesion, cell migration and cell survival. The authors have previously demonstrated that paxillin is overexpressed in lung cancer tissues and identified somatic paxillin mutations in 9% of lung cancers. A murine in vivo xenograft model of the most common paxillin mutation (A127T) showed increased cell proliferation and invasive tumour growth, establishing an important role for paxillin in the development of lung cancer.


METHODS
The authors analysed 279 bronchoscopy-aided biopsy specimens from 92 high-risk patients. Adenocarcinoma with bronchioloalveolar features and pure bronchioloalveolar carcinoma (BAC) were analysed with fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC).


RESULTS
Paxillin is overexpressed in premalignant areas of hyperplasia, squamous metaplasia and goblet cell metaplasia, as well as dysplastic lesions and carcinoma in high-risk patients. Concordance between increased paxillin gene copy number and paxillin overexpression was observed in cases of adenocarcinoma eusomic for chromosome 12.


CONCLUSIONS
Paxillin overexpression occurs during the earliest stages of lung cancer development. FISH and IHC analysis of lung adenocarcinoma suggests that relatively small-scale genomic rearrangements of chromosome 12 are associated with paxillin overexpression in lung adenocarcinoma.
Department of Pathology, University of Chicago Medical Center, Chicago, Illinois 60637, USA. alexander.mackinnon@uchospitals.edu
Alexander C
AC
Mackinnon
Maria
M
Tretiakova
Les
L
Henderson
Rajendra G
RG
Mehta
Benjamin C
BC
Yan
Loren
L
Joseph
Thomas
T
Krausz
Aliya N
AN
Husain
Mary E
ME
Reid
Ravi
R
Salgia
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D000077192:Adenocarcinoma of Lung; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D000368:Aged; D001706:Biopsy; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D018773:Genes, erbB-1 / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D051419:Paxillin / Q000235:genetics / Q000378:metabolism*; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
C117307:KRAS protein, human; D009363:Neoplasm Proteins; C496061:PXN protein, human; D051419:Paxillin; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins