Background
Angiogenesis is an essential biologic event in the pathogenesis of human malignancies.
We postulated that expression analysis of genes that modulate angiogenesis would identify
differentially expressed genes that would help to distinguish benign from malignant
thyroid neoplasms and serve as markers of aggressive differentiated thyroid cancer.
Methods
A complementary DNA (cDNA) array with 96 genes that modulate angiogenesis was used
to identify differentially expressed genes (2-fold higher or lower) in malignant versus
benign thyroid neoplasms. Real-time quantitative polymerase chain reaction was used
to confirm cDNA array expression data in 123 patients (4 normal thyroid, 26 hyperplastic
nodules, 27 follicular adenomas, 23 follicular cancers, 18 follicular variant of papillary
cancers, 25 papillary cancers).
Results
Twenty-two genes were upregulated in malignant thyroid neoplasms by cDNA array analysis,
but only 13 genes had higher messenger RNA (mRNA) expression levels in malignant than
in benign thyroid neoplasms by real-time quantitative polymerase chain reaction (P ≤ .04). Of the 13 differentially expressed genes, the combined use of angiopoietin
2 (ANGPT2) and tissue inhibitor of metalloproteinase 1 (TIMP1) mRNA expression levels
was best for distinguishing malignant from benign thyroid neoplasms, with a sensitivity
of 90%, specificity of 85%, positive predictive value of 75%, and negative predictive
value of 94%. Epidermal growth factor receptor and ephrin B2 mRNA expression was elevated
in higher TNM stage neoplasms and in patients with high-risk AMES (Age, distant Metastasis,
Extrathyroidal invasion, and tumor Size) differentiated thyroid cancers (P ≤ .005).
Conclusions
Angiopoietin 2 and tissue inhibitor of metalloproteinase 1 are diagnostic markers
of malignant thyroid nodules and could improve the diagnostic accuracy of FNA biopsy.
Epidermal growth factor receptor and ephrin B2 are markers of aggressive differentiated
thyroid cancer.
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Article info
Publication history
San Francisco, Calif
Footnotes
Presented at the 26th Annual Meeting of the American Association of Endocrine Surgeons, Cancun, Mexico, April 3-5, 2005.
Supported in part by the University of California Cancer Research Coordinating Committee, the Harold Amos Medical Faculty Development Program of the Robert Wood Johnson Foundation, and a Hellman Family Grant.
Identification
Copyright
© 2005 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
