8 research outputs found
Recurrent genomic gains in preinvasive lesions as a biomarker of risk for lung cancer.
Lung carcinoma development is accompanied by field changes that may have diagnostic significance. We have previously shown the importance of chromosomal aneusomy in lung cancer progression. Here, we tested whether genomic gains in six specific loci, TP63 on 3q28, EGFR on 7p12, MYC on 8q24, 5p15.2, and centromeric regions for chromosomes 3 (CEP3) and 6 (CEP6), may provide further value in the prediction of lung cancer. Bronchial biopsy specimens were obtained by LIFE bronchoscopy from 70 subjects (27 with prevalent lung cancers and 43 individuals without lung cancer). Twenty six biopsies were read as moderate dysplasia, 21 as severe dysplasia and 23 as carcinoma in situ (CIS). Four-micron paraffin sections were submitted to a 4-target FISH assay (LAVysion, Abbott Molecular) and reprobed for TP63 and CEP 3 sequences. Spot counts were obtained in 30-50 nuclei per specimen for each probe. Increased gene copy number in 4 of the 6 probes was associated with increased risk of being diagnosed with lung cancer both in unadjusted analyses (odds ratio = 11, p<0.05) and adjusted for histology grade (odds ratio = 17, p<0.05). The most informative 4 probes were TP63, MYC, CEP3 and CEP6. The combination of these 4 probes offered a sensitivity of 82% for lung cancer and a specificity of 58%. These results indicate that specific cytogenetic alterations present in preinvasive lung lesions are closely associated with the diagnosis of lung cancer and may therefore have value in assessing lung cancer risk
Chromosomal Aneusomy in Bronchial High-Grade Lesions Is Associated with Invasive Lung Cancer
Rationale: The development of lung cancer (LC) is accompanied by field changes in the airway mucosa that may have prognostic importance
Association between disease status and abnormal FISH marker (>2 copies per cell) for the top 4 markers (CEP3, <i>TP63</i>, CEP6, <i>MYC</i>).
*<p>Adjusted by multiple logistic regression for gender, age, center, current smoking status and histologic grade.</p
Percentage of lesions with abnormal FISH copy numbers according to case or control status (70 subjects).
*<p>Adjusted by multiple logistic regression for gender, age, center, and current smoking status.</p
Receiver operating characteristic curves describing the diagnostic prediction accuracy of three models, demographics alone (plain line, area under the curve (AUC) 73.4%), in combination with cytology (dashed line, AUC 86.6%) or demographics in combination with cytology and 4 FISH biomarker candidates (dotted line, AUC 92.6%).
<p>The demographic information represents gender, age, pack years smoking history, and smoking status.</p
Distribution of lung cancer cases and controls according to demographic and histology variables.
<p>Distribution of lung cancer cases and controls according to demographic and histology variables.</p