Computerized analysis of cytology and fluorescence in situ hybridization (FISH) in induced sputum for lung cancer detection.
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.
Guber
Alexander
A
Pulmonary Department, Meir Hospital, Kfar Saba, Israel.
Greif
Joel
J
Rona
Roni
R
Fireman
Elizabeth
E
Madi
Lea
L
Kaplan
Tal
T
Yemini
Zipi
Z
Gottfried
Maya
M
Katz
Ruth L
RL
Daniely
Michal
M
D014408:Biomarkers, Tumor / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D003581:Cytodiagnosis / Q000379:methods; D003936:Diagnosis, Computer-Assisted / Q000379:methods; D005240:Feasibility Studies; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics; D015203:Reproducibility of Results; D012269:Ribosomal Proteins / Q000235:genetics; D012680:Sensitivity and Specificity; D013183:Sputum / Q000378:metabolism*
D014408:Biomarkers, Tumor; D037662:Pulmonary Surfactant-Associated Protein A; D012269:Ribosomal Proteins; C445842:SFTPA1 protein, human; C445843:SFTPA2 protein, human; C041174:ribosomal protein L14