Diagnostic Utility of IMP3 Expression in Thyroid Neoplasms: A Real-Time PCR Study
KM Rumilla, L Jin, LA Erickson, J Zhang, RV Lloyd. Mayo Clinic, Rochester, MN
Background: Immunohistochemical detection of insulin-like growth factor II mRNA binding protein 3 (IMP3) expression levels has recently been found to be a useful marker in differentiating follicular adenoma from follicular variant of papillary thyroid carcinoma and follicular carcinoma. IMP3 is a regulator of insulin-like growth factor 2 expression and is active in embryonic tissues during development but not in adult tissues. IMP3 appears to play a significant role in the neoplastic process of a number of tissues including thyroid follicular cells. Its potential role in assisting in the distinction between benign and malignant well differentiated thyroid tumors was explored by real-time PCR.
Design: A total of 106 thyroid neoplasms were collected from the pathology files between 1980-2008, including: follicular adenomas (FA) n=22, follicular carcinomas (FTC) n=14, papillary thyroid carcinomas (PTC) n=28, follicular variant of papillary thyroid carcinoma (FVPTC) n=11, Hurthle cell adenomas (HA) n=10, and Hurthle cell carcinomas (HCA) n=21. RNA was extracted from formalin fixed paraffin embedded tissue. Real-time PCR primers and probes were designed with a fluorescent tag. Real-time PCR was performed on a LC480; samples were tested in triplicate in a 20 microliter reaction volume with 200 ng of RNA. Phosphoglycerol kinase was used as an RNA control, and a pool of three normal thyroids were used for calibration and to calculate the fold change in expression over normal.
Results: IMP3 mRNA expression in all tumors was elevated compared to normal thyroid tissue: FA 2.8 fold increase, FTC 22.2 fold increase, FVPTC 47.4 fold increase, PTC 44.7 fold increase, HA 11.6 fold increase, and HCA 12.1 fold increase. Using a cut off of 7.4 fold the sensitivity and specificity of IMP3 for the whole group was 81% and 81% respectively. However, for the non-Hurthle tumors the sensitivity was 92% and the specificity was 95% compared to that for the Hurthle cell tumors, 52% and 50% respectively. The positive predictive value and negative predictive value of IMP3 in the overall cohort was 91% and 65%, while among the non-Hurthle cell tumors it was 98% and 84% respectively and in the Hurthle cell tumors it was 69% and 33% respectively.
Conclusions: IMP3 mRNA expression is helpful in distinguishing between benign and malignant follicular and papillary thyroid tumors. However, IMP3 is not a useful marker to distinguish benign and malignant Hurthle cell tumors.
Category: Head & Neck
Tuesday, March 23, 2010 11:30 AM
Platform Session: Section G, Tuesday Morning