Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia as a Precursor to Pulmonary Neuroendocrine Tumors * Chest 2004;125;108S DOI 10.1378/chest.125.5_suppl.108S The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/125/5_suppl/108S.full.html
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cell specificity of the amplification. Precise real-time quantitation of the expression of these genes employs ratios of target crossover point to reference housekeeper CRO (LightCycler; Roche; Basel, Switzerland). Genes that were analyzed included the aromatic hydrocarbon receptor gene (Ahr), cytochrome P450 genes CYP1A1 and CYP1B1, glutathione-S-transferase genes GSTM1, GSTM3, GSTP1, and GSTT1, nicotinamide adenine dinucleotide phosphate-quinone oxidoreductase (NQO1), copper-zinc superoxide dismutase (CuZn-SOD), catalase (CAT), and glutathione peroxidase (GPx). For any given individual among our initial group of human subjects, we have been able to reliably quantitate gene expression in the buccal cytologic specimens. We have compared buccal gene expression to laser capture microdissected lung gene expression, both by identical techniques of real-time quantitative reverse transcription polymerase chain reaction.
Results We have found close concordance of phase I, phase II, and antioxidant genes in constitutive expression (not expressed, CYP1A1, GSTM1, and GSTM3; all expressed, GSTP1, GSTT1; NQO1, SOD, CAT, and GPx) between the two tissues. There is often buccal-lung discordance for the Ahr gene. However, for all 11 transcripts studied in our first 11 individuals to date, 88 to 96% of the genespecific buccal-lung expression comparisons have shown qualitatively concordant expression (2 ⫽ 62.4; p ⬍ 0.001). The quantitative covariation between the two tissues is under study.
Conclusion We have in preliminary fashion shown that (1) gene expression is quantifiable in cytologically collected buccal cells, and (2) there appears to be good concordance between those carcinogen and oxidant metabolism genes expressed in the buccal mucosa and those expressed in the laser microdissected human lung epithelium. We have enlarged the group undergoing buccal-lung comparison, and have commenced stratification of the expression data for covariation with tobacco exposure, to define each individual’s unique gene expression signature in this cancer-relevant pathway.
n 1992, Aguayo et al described six patients with slowly I progressive cough and breathlessness, obstructive and/ 1
or restrictive respiratory impairment, and diffuse reticulonodular infiltrates seen on thoracic tomographic scanning, in whom a pulmonary biopsy revealed widespread intraluminal and extraluminal proliferation of pulmonary neuroendocrine cells (PNCs) in all patients, accompanied by peripheral carcinoid tumors in three patients. There was submucosal fibrosis of affected airways, but none of the conditions usually associated with the reactive proliferation of PNCs was evident. This and subsequent studies have further defined the clinical and pathologic parameters of this rare condition, now conventionally known as diffuse idiopathic PNC hyperplasia or DIPNECH. DIPNECH raises interesting questions about the relationship between the proliferation of PNCs, hitherto considered a reactive process, and the genesis of bona fide pulmonary neuroendocrine tumors (PNTs), such that it now appears as a preneoplastic condition in the latest World Health Organization histologic classification of tumors of the lung and pleura. However, the carcinoid tumors that accompany DIPNECH and are presumed to develop from it appear to be invariably peripheral and always of low grade. The disease runs a chronic, indolent course, and the emergence from DIPNECH of PNTs in the central airways or of higher grades of malignancy has not been described. It is probable, therefore, that DIPNECH is a precursor exclusively of typical carcinoid tumors in a peripheral location. In this regard, it may be related to the more localized and less florid proliferation of PNCs that are commonly seen in the vicinity of such tumors. A role for the condition as a precursor to the predominantly central, high-grade PNTs (ie, the large cell and small cell neuroendocrine carcinomas) seems unlikely, however, any precursor to these more common and dangerous tumors remains unknown.
Reference 1 Aguayo SM, Miller YE, Waldron JA, et al. Brief report: idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells and airways disease. N Engl J Med 1992; 327:1285–1288
Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia as a Precursor to Pulmonary Neuroendocrine Tumors* John R. Gosney, BSc, MD
(CHEST 2004; 125:108S) Abbreviations: DIPNECH ⫽ diffuse idiopathic PNC hyperplasia; PNC ⫽ pulmonary neuroendocrine cell; PNT ⫽ pulmonary neuroendocrine tumor 108S
*From the Royal Liverpool University Hospital, Liverpool, UK. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail:
[email protected]). Correspondence to: J.R. Gosney, BSc, MD, Department of Pathology, 5th floor, Duncan Bldg, Royal Liverpool University Hospital, Daulby St, Liverpool L69 3GA, UK; e-mail: j.gosney@ rlbuh-tr.nwest.nhs.uk
Thomas L. Petty 46th Annual Aspen Lung Conference; Lung Cancer: Early Events, Early Interventions
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Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia as a Precursor to Pulmonary Neuroendocrine Tumors * Chest 2004;125; 108S DOI 10.1378/chest.125.5_suppl.108S This information is current as of May 23, 2011 Updated Information & Services Updated Information and services can be found at: http://chestjournal.chestpubs.org/content/125/5_suppl/108S.full.html Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.chestpubs.org/site/misc/reprints.xhtml Reprints Information about ordering reprints can be found online: http://www.chestpubs.org/site/misc/reprints.xhtml Citation Alerts Receive free e-mail alerts when new articles cite this article. To sign up, select the "Services" link to the right of the online article. Images in PowerPoint format Figures that appear in CHEST articles can be downloaded for teaching purposes in PowerPoint slide format. See any online figure for directions.
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