title: Persistence of Bronchial Dysplasia Is Associated with Development of Invasive Squamous Cell Carcinoma.
abstract: Bronchial dysplasia (BD), a presumed precursor of pulmonary squamous cell carcinoma (SCC), rarely progresses to invasive cancer. A high-risk cohort at the University of Colorado provided an opportunity to directly sample airway epithelium at mapped sites on successive bronchoscopies. We have hypothesized that persistent dysplastic lesions showing a similar or higher level of dysplasia on follow-up biopsy, are associated with increased risk for the development of SCC. Endoscopic biopsies from 188 high-risk subjects were histologically classified according to the current WHO classification for BD using a numeric histology score ranging from 1 to 8 representing normal bronchial mucosa through invasive lung cancer. Differences in follow-up histology scores were compared between sites classified by clinical, histologic, and immunohistochemical variables. Subjects with a higher frequency of sites that persist or progress to high-grade dysplasia (≥37.5% persist/progress, N = 35 versus <37.5% persist/progress, N = 114) show a significant association with development of incident invasive SCC (adjusted HR, 7.84; 95% confidence interval, 1.56-39.39), and those with incident lung SCC have adjusted mean follow-up histology scores 1.55 U higher than in subjects without lung cancer. Current smoking, elevated Ki67 growth fraction, histologic features of angiogenic squamous dysplasia (ASD) and higher histology score in baseline biopsies are significantly associated with increased follow-up histology scores. These results show that persistent BD is associated with the development of invasive SCC. Furthermore, increased expression of Ki67, the presence of angiogenic change and degree of baseline atypia are associated with persistence of BD.
authors.affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. dan.merrick@ucdenver.edu.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Merrick
authors.affiliation: Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Dexiang
authors.initials: D
authors.lastname: Gao
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, Denver Veterans Affairs Medical Center, Denver, Colorado. Division of Pulmonary Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: York E
authors.initials: YE
authors.lastname: Miller
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, Denver Veterans Affairs Medical Center, Denver, Colorado. Division of Pulmonary Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Keith
authors.affiliation: Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Baron
authors.affiliation: Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado.
authors.forename: William
authors.initials: W
authors.lastname: Feser
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Kennedy
authors.affiliation: Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Blatchford
authors.affiliation: Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado.
authors.forename: Sarah
authors.initials: S
authors.lastname: Braudrick
authors.affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
authors.affiliation: Department of Craniofacial Biology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Lynn
authors.initials: L
authors.lastname: Heasley
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Bunn
authors.affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Wilbur A
authors.initials: WA
authors.lastname: Franklin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000473:pathology*; D015331:Cohort Studies; D018450:Disease Progression; D004724:Endoscopy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008171:Lung Diseases / Q000150:complications / Q000473:pathology*; D008175:Lung Neoplasms / Q000150:complications / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic
chemical_list: D019394:Ki-67 Antigen