IQGAP1 Copy Number in Follicular-Patterned Lesions of the Thyroid – A Pilot Study
Ann E Walts, Amin Riley-Portuges, Shikha Bose. Cedars-Sinai Medical Center, Los Angeles, CA
Background: The accuracy and reproducibility of the diagnosis of follicular-patterned thyroid lesions (FPTL) is currently limited by subjective morphological criteria and difficulties in assessing capsular integrity and vascular invasion. IQGAP1 is a widely conserved multifunctionl protein currently thought to play an important role in cell polarity, adhesion, migration and proliferation through regulation of the actin microtubule cytoskeleton, transmembrane trafficking, and intracellular signaling. IQGAP1 genetic copy gain has recently been reported in association with increased invasiveness in some thyroid tumors. This pilot study was designed to explore the potential role of IQGAP1 copy number (CN) in the diagnosis of FPTL.
Design: 27 FPTL [10 follicular adenomas (FA), 10 follicular variants of papillary carcinoma (FVPTC), and 7 follicular carcinomas (2 invasive, 3 minimally invasive, and 2 metastases) (FC)] were retrieved from our files. After slides were reviewed and diagnoses confirmed, DNA was extracted from selected areas of two 10-micron sections of each lesion using standard Qiagen QiaAmp FFPE extraction (Valencia CA). Real time PCR detection of gene specific primers (IQGAP1 and a reference gene RNAase) was accomplished using MGB probes (Applied Biosystems). CN was calculated for each sample using the linear region of a standard curve established from a serial dilution and linear regression curve. Histological diagnoses were correlated with CN.
Results: IQGAP1 CN ranged from 1.7 to 3.9. Using a cut-off CN ≥2.5, 2 (20%) of 10 FA, 4 (40%) of 10 FVPTC, and 4 (57%) of 7 FC were positive. Although the percentage of cases with CN ≥2.5 increased from FA to FVPTC to FC, the differences in CN did not reach statistical significance (p>0.05) across the three diagnostic groups.
Conclusions: - Increasing percentages of cases with IQGAP1 CN ≥2.5 were observed when FA, FVPTC, and FC were compared.
- IQGAP1 CN may be helpful to stratify FPTL.
- Larger studies are warranted to further assess the potential role of IQGAP1 CN in the diagnosis of thyroid lesions.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 36, Tuesday Afternoon