Genetically abnormal circulating cells in lung cancer patients: an antigen-independent fluorescence in situ hybridization-based case-control study.
OBJECTIVE
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).


METHODS
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 by using an automated fluorescent scanner. Numbers of CACs were calculated based on the percentage of CACs (defined as PBMCs with genetic abnormalities) per milliliter of blood and expressed per microliter of blood.


RESULTS
Patients with NSCLC had significantly higher numbers of CACs than controls. Mean number of CACs ranged from 7.23 +/- 1.32/microL for deletions of 10q22.3/CEP10 to 45.52 +/- 7.49/microL 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.


CONCLUSIONS
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.
Katz
Ruth L
RL
Department of Pathology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. rkatz@mdanderson.org
He
Weigong
W
Khanna
Abha
A
Fernandez
Ricardo L
RL
Zaidi
Tanweer M
TM
Krebs
Matthew
M
Caraway
Nancy P
NP
Zhang
Hua-Zhong
HZ
Jiang
Feng
F
Spitz
Margaret R
MR
Blowers
David P
DP
Jimenez
Carlos A
CA
Mehran
Reza J
RJ
Swisher
Stephen G
SG
Roth
Jack A
JA
Morris
Jeffrey S
JS
Etzel
Carol J
CJ
El-Zein
Randa
R
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor