Identification of genes differentially expressed in benign versus malignant thyroid tumors.
OBJECTIVE
Although fine-needle aspiration biopsy is the most useful diagnostic tool in evaluating a thyroid nodule, preoperative diagnosis of thyroid nodules is frequently imprecise, with up to 30% of fine-needle aspiration biopsy cytology samples reported as "suspicious" or "indeterminate." Therefore, other adjuncts, such as molecular-based diagnostic approaches are needed in the preoperative distinction of these lesions.


METHODS
In an attempt to identify diagnostic markers for the preoperative distinction of these lesions, we chose to study by microarray analysis the eight different thyroid tumor subtypes that can present a diagnostic challenge to the clinician.


RESULTS
Our microarray-based analysis of 94 thyroid tumors identified 75 genes that are differentially expressed between benign and malignant tumor subtypes. Of these, 33 were overexpressed and 42 were underexpressed in malignant compared with benign thyroid tumors. Statistical analysis of these genes, using nearest-neighbor classification, showed a 73% sensitivity and 82% specificity in predicting malignancy. Real-time reverse transcription-PCR validation for 12 of these genes was confirmatory. Western blot and immunohistochemical analyses of one of the genes, high mobility group AT-hook 2, further validated the microarray and real-time reverse transcription-PCR data.


CONCLUSIONS
Our results suggest that these 12 genes could be useful in the development of a panel of markers to differentiate benign from malignant tumors and thus serve as an important first step in solving the clinical problem associated with suspicious thyroid lesions.
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Nijaguna B
NB
Prasad
Helina
H
Somervell
Ralph P
RP
Tufano
Alan P B
AP
Dackiw
Michael R
MR
Marohn
Joseph A
JA
Califano
Yongchun
Y
Wang
William H
WH
Westra
Douglas P
DP
Clark
Christopher B
CB
Umbricht
Steven K
SK
Libutti
Martha A
MA
Zeiger
D014408:Biomarkers, Tumor / Q000235:genetics*; D044963:Biopsy, Fine-Needle; D015153:Blotting, Western; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013959:Thyroid Diseases / Q000175:diagnosis / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000235:genetics*; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor