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1.  Automated detection of genetic abnormalities combined with cytology in sputum is a sensitive predictor of lung cancer 
Modern Pathology  2008;21(8):950-960.
Detection of lung cancer by sputum cytology has low sensitivity but is noninvasive and, if improved, could be a powerful tool for early lung cancer detection. To evaluate whether the accuracy of diagnosing lung cancer by evaluating sputa for cytologic atypia and genetic abnormalities is greater than that of conventional cytology alone, automated scoring of genetic abnormalities for 3p22.1 and 10q22.3 (SP-A) by fluorescence in situ hybridization (FISH) and conventional cytology was done on sputa from 35 subjects with lung cancer, 25 high-risk smokers, and 6 healthy control subjects. Multivariate analysis was performed to select variables that most accurately predicted lung cancer. A model of probability for the presence of lung cancer was derived for each subject. Cells exfoliated from patients with lung cancer contained genetic aberrations and cytologic atypias at significantly higher levels than in those from control subjects. When combined with cytologic atypia, a model of risk for lung cancer was derived that had 74% sensitivity and 82% specificity to predict the presence of lung cancer, whereas conventional cytology achieved only 37% sensitivity and 87% specificity. For diagnosing lung cancer in sputum, a combination of molecular and cytologic variables was superior to using conventional cytology alone.
PMCID: PMC3377448  PMID: 18500269
surfactant protein A gene; 3p22.1; FISH; cytology; field cancerization effect; sputum
2.  Fluorescence in situ hybridization for detecting urothelial carcinoma: A clinicopathological study 
Cancer cytopathology  2010;118(5):259-268.
Because urothelial carcinoma (UC) is associated with a significant high risk of recurrence and progression, patients with UC require long-term surveillance. Fluorescence in situ hybridization (FISH) has been shown to be more sensitive than cytology in the detection of UC. This study evaluated the use of FISH for detecting UC.
We used a pathology database to identify patients who had urine cytology and FISH performed at our institution between 2004 and 2006. Urinary specimens were analyzed using UroVysion FISH probes for abnormalities in centromeric chromosomes 3, 7 and 17 and locus specific 9p21. FISH results were correlated with cytologic findings and a minimal clinical follow-up of 24 months.
We identified 1006 consecutive urinary specimens from 600 patients (448 men and 152 women) who were monitored for recurrent UC (915 specimens) or evaluated for urinary symptoms (91 specimens). On FISH analysis, 669 specimens were negative for UC and 272 specimens were positive for UC. Sixty-five (6%) specimens were insufficient for FISH analysis. The sensitivity and specificity of FISH for UC were 58% and 66%, respectively, and 59% and 63% when FISH and cytology results were combined. Factors contributing to decreased FISH sensitivity included the paucity or absence of tumor cells, low-grade tumors, degenerated cells, method of specimen collection, type of specimen, and obscuring inflammatory cells or lubricant.
We found UroVysion FISH had good sensitivity and specificity for detecting UC in urinary specimens. It is important to correlate the FISH results with the cytologic findings.
PMCID: PMC2993817  PMID: 20665656
Urothelial carcinoma; fluorescence in situ hybridization; chromosomal abnormalities; urine; cytology; multitarget FISH; bladder neoplasms; UroVysion
3.  Genetically Abnormal Circulating Cells in Lung Cancer Patients: An Antigen Independent Fluorescence in-situ Hybridization Based Case-Control Study 
We performed a study to determine if a fluorescence in-situ hybridization (FISH)-based assay using isolated peripheral blood mononuclear cells (PBMCs) with DNA probes targeting specific sites on chromosomes known to have abnormalities in Non Small Cell Lung Cancer (NSCLC) cases could detect circulating genetically abnormal cells (CACs).
Experimental Design
We evaluated 59 NSCLC cases with stage I through IV disease and 24 controls. PBMCs and matched tumors were hybridized with 2 two-color (3p22.1/CEP3 and 10q22.3 [SP-A]/CEP10) and 2 four-color (CEP3, CEP7, CEP17, and 9p21.3 [URO]) and (EGFR, c-MYC, 6p11-q11, and 5p15.2 [LAV]) FISH probes. Percentages of cytogenetically abnormal cells (CACs) in peripheral blood and in matched tumor specimens were quantified using an automated fluorescent scanner. Numbers of CACs were calculated based on the percentage of CACs (defined as PBMCs with genetic abnormalities) per mL of blood and expressed per microliter of blood.
Patients with NSCLC had significantly higher numbers of CACs than did controls. Mean number of CACs ranged from 7.23±1.32/μl for deletions of 10q22.3/CEP10 to 45.52±7.49/μl for deletions of 3p22.1/CEP3. Numbers of CACs with deletions of 3p22.1, 10q22.3, and 9p21.3, and gains of URO, increased significantly from early to advanced stage of disease.
We have developed a sensitive and quantitative antigen-independent FISH-based test for detecting CACs in peripheral blood of patients with NSCLC which showed a significant correlation with the presence of cancer. If this pilot study can be validated in a larger study, CACs may have a role in the management of patients with NSCLC.
PMCID: PMC2949278  PMID: 20651054

Results 1-3 (3)