-
Am. J. Respir. Crit. Care Med. · Oct 2011
DNA copy number alterations in endobronchial squamous metaplastic lesions predict lung cancer.
- Katrien Grünberg, Pieter E Postmus, Robert A A van Boerdonk, Thomas G Sutedja, Peter J F Snijders, Emilie Reinen, Saskia M Wilting, Mark A van de Wiel, F Erik B J M Thunnissen, Sylvia Duin, Clarissa Kooi, Bauke Ylstra, Chris J L M Meijer, Gerrit A Meijer, Johannes M A Daniels, Egbert F Smit, and Daniëlle A M Heideman.
- VU University Medical Center, Department of Pathology, De Boelelaan 1117, Amsterdam, The Netherlands.
- Am. J. Respir. Crit. Care Med.. 2011 Oct 15;184(8):948-56.
RationaleAutofluorescence bronchoscopy (AFB) is a valid strategy for detecting premalignant endobronchial lesions. However, no biomarker can reliably predict lung cancer risk of subjects with AFB-visualized premalignant lesions.ObjectivesThe present study set out to identify AFB-visualized squamous metaplastic (SqM) lesions with malignant potential by DNA copy number profiling.MethodsRegular AFB examinations in 474 subjects at risk of lung cancer identified six subjects with SqM lesions at baseline, and carcinoma in situ or carcinoma (carcinoma in situ or greater) at the initial SqM site at follow-up bronchoscopy. These progressive SqM lesions were compared for immunostaining pattern and array comparative genomic hybridization-based chromosomal profiles with 23 SqM lesions of subjects who remained cancer-free. Specific DNA copy number alterations (CNAs) linked to cancer risk were identified and accuracy of CNAs to predict endobronchial cancer in this series was determined.Measurements And Main ResultsAt baseline, p53, p63, and Ki-67 immunostaining were not predictive for a differential clinical outcome of SqM lesions. The mean number of CNAs in baseline SqM of cases was significantly higher compared with control subjects (P < 0.01). Chromosomal regions significantly more frequently altered in SqM of cases were 3p26.3-p11.1, 3q26.2-q29, 9p13.3-p13.2, and 17p13.3-p11.2 (family-wise error rate <0.10). CNAs were specifically detected at the site of future cancer. In cases, baseline-detected CNAs persisted in subsequent biopsies taken from the initial site, and levels increased toward cancer progression. In this series, a model based on CNAs at 3p26.3-p11.1, 3q26.2-29, and 6p25.3-24.3 predicted cancer with 97% accuracy.ConclusionsThe data suggest that the presence of specific CNAs in SqM lesions predict endobronchial cancer.
Notes
Knowledge, pearl, summary or comment to share?You can also include formatting, links, images and footnotes in your notes
- Simple formatting can be added to notes, such as
*italics*
,_underline_
or**bold**
. - Superscript can be denoted by
<sup>text</sup>
and subscript<sub>text</sub>
. - Numbered or bulleted lists can be created using either numbered lines
1. 2. 3.
, hyphens-
or asterisks*
. - Links can be included with:
[my link to pubmed](http://pubmed.com)
- Images can be included with:

- For footnotes use
[^1](This is a footnote.)
inline. - Or use an inline reference
[^1]
to refer to a longer footnote elseweher in the document[^1]: This is a long footnote.
.