Genomic instability measurement in the diagnosis of thyroid neoplasms.
BACKGROUND
Clinically palpable thyroid nodules are present in approximately 10% of the population, although only 5% to 7% of these nodules harbor malignancy. Fine-needle aspiration has become one of the central tools in the diagnostic armamentarium of the surgeon/endocrinologist. There is, however, up to a 30% indeterminate diagnostic rate associated with this technique, resulting in unnecessary surgical interventions for patients harboring benign disease. A second issue of clinical importance is the unreliability of predicting outcomes based either on histologic findings alone or in combination with clinical staging. To address these diagnostic and clinical shortcomings, we have used measurement of genomic instability as a diagnostic and prognostic indicator for thyroid neoplasms.


METHODS
Genomic instability of thyroid tissue samples was determined by inter-(simple sequence repeat) PCR, microsatellite instability analysis, and fluorescence in situ hybridization (FISH) on thyroid neoplasms from 22 patients.


RESULTS
Inter-(simple sequence repeat) PCR detected genomic instability with an index range 0% to 1.9% (mean, 0.56%) in patients with benign disease, whereas in patients with malignant histologic findings the values ranged from 0% to 6.6% (mean, 2.9%). This difference between benign and malignant values was statistically significant (p =.004). There was no demonstrable microsatellite instability or loss of heterozygosity for six markers examined in this group. Losses of chromosomes 17 and X in benign disease and gains of chromosomes 7, 12, 17, and X in Hurthle cell carcinoma were observed, although not at a significant rate.


CONCLUSIONS
Genomic instability as measured by inter-(simple sequence repeat) PCR was significantly higher for malignant diseases compared with benign thyroid tissues, but no such association was seen with aneuploidy or microsatellite instability.
Stoler
Daniel L
DL
Department of Experimental Pathology, Roswell Park Cancer Institute, Buffalo, New York, USA.
Datta
Rajiv V
RV
Charles
Melita A
MA
Block
AnneMarie W
AW
Brenner
Bruce M
BM
Sieczka
Elizabeth M
EM
Hicks
Wesley L
WL
Loree
Thom R
TR
Anderson
Garth R
GR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000782:Aneuploidy; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000235:genetics*
D004273:DNA, Neoplasm; D005819:Genetic Markers