ABSTRACT
BACKGROUND: Lung cancer results from a multistep process, whereby genetic and epigenetic alterations lead to a malignant phenotype. Somatic mutations, deletions, and amplifications can be detected in the tumor itself, but they can also be found in histologically normal bronchial epithelium as a result of field cancerization. The present feasibility study describes a computer-assisted analysis of induced sputum employing morphology and fluorescence in situ hybridization (target-FISH), using 2 biomarkers located at chromosomes 3p22.1 and 10q22.3. METHODS: Induced sputum samples were collected using a standardized protocol from 12 patients with lung cancer and from 15 healthy, nonsmoking controls. We used an automated scanning system that allows consecutive scans of morphology and FISH of the same slide. Cells derived for the lower airways were analyzed for the presence of genetic alterations in the 3p22.1 and 10q22.3 loci. RESULTS: The cutoff for a positive diagnosis was defined as >4% of cells showing genetic alterations. Eleven of 12 lung cancer patients and 12 of 15 controls were identified correctly, giving an overall sensitivity and specificity of 91.66% and 80%, respectively. CONCLUSIONS: This study describes a new technology for detecting lung cancer noninvasively in induced sputum via a combination of morphology and FISH analysis (target-FISH) using computer-assisted technology. This approach may potentially be utilized for mass screening of high-risk populations.
Subject(s)
Biomarkers, Tumor/genetics , In Situ Hybridization, Fluorescence/methods , Lung Neoplasms/genetics , Sputum/metabolism , Chromosomes, Human, Pair 10/genetics , Chromosomes, Human, Pair 3/genetics , Cytodiagnosis/methods , Diagnosis, Computer-Assisted/methods , Feasibility Studies , Female , Genetic Testing/methods , Humans , Lung Neoplasms/diagnosis , Male , Pulmonary Surfactant-Associated Protein A/genetics , Reproducibility of Results , Ribosomal Proteins/genetics , Sensitivity and SpecificityABSTRACT
BACKGROUND: Bladder cancer is among the 5 most common malignancies worldwide. Patients with bladder cancer are closely followed with periodic cystoscopies and urine cytology analyses due to the significant risk of tumor recurrence. The UroVysion fluorescence in situ hybridization (FISH) test demonstrated higher sensitivity over urine cytology in detecting bladder cancer by most comparative studies. METHODS: In the current study, the diagnostic usefulness of a combined cytology and FISH analysis approach was tested using the Duet automatic scanning system in patients with benign urine cytology who were being monitored for recurrent urothelial carcinoma or being assessed for various urologic symptoms. RESULTS: By combining the benefits of conventional cytology with molecular diagnostics, a more sensitive detection of bladder cancer was attained. All patients who had positive cystoscopy concomitantly with urine sampling were detected by combined analysis. Additional patients that developed transitional cell carcinoma during a follow-up period of 24 months had a previous positive result on combined analysis. Only 2 patients with a negative combined analysis result presented with late disease recurrence (20 months and 22 months, respectively, after the negative test). Therefore, negative combined analysis was found to be predictive of a lack of disease recurrence for at least 12 months. In this timeframe, the overall sensitivity, specificity, negative predictive value (NPV), and positive predictive values of the combined analysis test were 100%, 65%, 100%, and 44%, respectively. CONCLUSIONS: Given the absolute sensitivity and NPV of the combined analysis test, the management of patients with a negative combined analysis result might be revised and allow for more flexible assessment and management of bladder cancer patients relying more on urine bound tests.
