DNA copy number aberrations in endobronchial lesions: a validated predictor for cancer.
We recently identified a DNA copy number aberration (CNA)-based classifier, including changes at 3p26.3-p11.1, 3q26.2-29, and 6p25.3-24.3, as a risk predictor for cancer in individuals presenting with endobronchial squamous metaplasia. The current study was set out to validate the prediction accuracy of this classifier in an independent series of endobronchial squamous metaplastic and dysplastic lesions. The study included 36 high-risk subjects who had endobronchial lesions of various histological grades that were identified and biopsied by autofluorescence bronchoscopy and were subjected to arrayCGH in a nested case-control design. Of the 36 patients, 12 had a carcinoma in situ or invasive carcinoma at the same site at follow-up (median 11 months, range 4-24), while 24 controls remained cancer free (78 months, range 21-142). The previously defined CNA-based classifier demonstrated 92% (95% CI 77% to 98%) accuracy for cancer (in situ) prediction. All nine subjects with CNA-based classifier-positive endobronchial lesions at baseline experienced cancer outcome, whereas all 24 controls and 3 cases were classified as being low risk. In conclusion, CNAs prove to be a highly accurate biomarker for assessing the progression risk of endobronchial squamous metaplastic and dysplastic lesions. This classifier could assist in selecting subjects with endobronchial lesions who might benefit from more aggressive therapeutic intervention or surveillance.
Department of Pathology, VU University Medical Center, , Amsterdam, The Netherlands.
Robert A A
RA
van Boerdonk
Johannes M A
JM
Daniels
Peter J F
PJ
Snijders
Katrien
K
Grünberg
Erik
E
Thunnissen
Mark A
MA
van de Wiel
Bauke
B
Ylstra
Pieter E
PE
Postmus
Chris J L M
CJ
Meijer
Gerrit A
GA
Meijer
Egbert F
EF
Smit
Thomas G
TG
Sutedja
Daniëlle A M
DA
Heideman
D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D001999:Bronchoscopy; D002278:Carcinoma in Situ / Q000175:diagnosis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors
D004273:DNA, Neoplasm; D005819:Genetic Markers
Airway Epithelium; Bronchoscopy; Lung Cancer