ALK-gene rearrangement: a comparative analysis on circulating tumour cells and tumour tissue from patients with lung adenocarcinoma.
BACKGROUND
A subgroup of anaplastic lymphoma kinase (ALK)-rearranged lung tumours can respond to ALK inhibitors. Until now, the ALK status in circulating tumour cells (CTCs) isolated from patients with lung cancer has not been characterised. We assessed the ALK status in CTCs detected in patients with lung cancer and correlated the results to the ALK status defined in the corresponding tumour tissue.


METHODS
A total of 87 patients with lung adenocarcinoma showing CTCs isolated using the isolation by size of epithelial tumour cell method were screened for their ALK status both in tumour samples and in CTCs. ALK break-apart fluorescence in situ hybridisation (FISH) and immunoreactivity analyses using an anti-ALK antibody (5A4 clone) were carried out on CTCs and compared with the results obtained in the corresponding tissue specimens.


RESULTS
A total of five patients showed ALK-gene rearrangement and strong ALK protein expression in CTCs and in the corresponding tumour samples. Both ALK-FISH and ALK immunoreactivity analyses show negative results in CTCs and corresponding tumour samples for 82 patients. Conclusions We demonstrated that the ALK status can be determined in CTCs isolated from patients with lung cancer by immunocytochemistry and FISH analyses. These results favour non-invasive, ALK-gene status pre-screening on a routine basis on CTCs isolated from patients with lung cancer and open new avenues for real-time monitoring for adapted targeted therapy.
Institute for Research on Cancer and Ageing (IRCAN), INSERM U1081, CNRS UMR 7284, Team 3, Nice; Team 3, Faculty of Medicine, University of Nice Sophia Antipolis, Nice; Human Biobank Unit; Laboratory of Clinical and Experimental Pathology, University Hospital Centre of Nice, Pasteur Hospital, Nice; Cancéropôle PACA, Marseille.
M
M
Ilie
Institute for Research on Cancer and Ageing (IRCAN), INSERM U1081, CNRS UMR 7284, Team 3, Nice; Team 3, Faculty of Medicine, University of Nice Sophia Antipolis, Nice; Laboratory of Clinical and Experimental Pathology, University Hospital Centre of Nice, Pasteur Hospital, Nice.
E
E
Long
Laboratory of Clinical and Experimental Pathology, University Hospital Centre of Nice, Pasteur Hospital, Nice.
C
C
Butori
Institute for Research on Cancer and Ageing (IRCAN), INSERM U1081, CNRS UMR 7284, Team 3, Nice; Team 3, Faculty of Medicine, University of Nice Sophia Antipolis, Nice; Human Biobank Unit; Laboratory of Clinical and Experimental Pathology, University Hospital Centre of Nice, Pasteur Hospital, Nice; Cancéropôle PACA, Marseille.
V
V
Hofman
Human Biobank Unit.
C
C
Coelle
Human Biobank Unit.
V
V
Mauro
Laboratory of Clinical and Experimental Pathology, University Hospital Centre of Nice, Pasteur Hospital, Nice.
K
K
Zahaf
Institute for Research on Cancer and Ageing (IRCAN), INSERM U1081, CNRS UMR 7284, Team 3, Nice; Team 3, Faculty of Medicine, University of Nice Sophia Antipolis, Nice; Department of Pneumology.
C H
CH
Marquette
Institute for Research on Cancer and Ageing (IRCAN), INSERM U1081, CNRS UMR 7284, Team 3, Nice; Team 3, Faculty of Medicine, University of Nice Sophia Antipolis, Nice; Department of Thoracic Surgery, University Hospital Centre of Nice, Pasteur Hospital, Nice.
J
J
Mouroux
University Réné Descartes, INSERM, Unit 807, Paris, France.
P
P
Paterlini-Bréchot
Institute for Research on Cancer and Ageing (IRCAN), INSERM U1081, CNRS UMR 7284, Team 3, Nice; Team 3, Faculty of Medicine, University of Nice Sophia Antipolis, Nice; Human Biobank Unit; Laboratory of Clinical and Experimental Pathology, University Hospital Centre of Nice, Pasteur Hospital, Nice; Cancéropôle PACA, Marseille. Electronic address: hofman.p@chu-nice.fr.
P
P
Hofman
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D000077547:Crizotinib; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D011379:Prognosis; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic
D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases