MicroRNA Profiling of Differentiated, Poorly Differentiated and Anaplastic Thyroid Carcinoma, a Comparative Approach
M Menon, S Schattgen, A Khan. UMassMemorial Medical Center, Worcester, MA
Background: MicroRNAs (miRNAs) belong to a class of small non-coding RNA species that are important regulators of a variety of biological processes including oncogenesis. Thyroid carcinomas encompass a wide spectrum ranging from differentiated thyroid carcinoma (DTC) to poorly differentiated (PDTC) and anaplastic thyroid carcinoma (ATC). DTC of both follicular and papillary types can progress to PDC and AC. The aim of our study was to evaluate if there is differential miRNA expression in various tumor subtypes during this progression.
Design: A search of the pathology archives over an 18-year period (1990-2008) retrieved 28 cases of PDTC. Tissue was available on 23 cases for the study, which included 15 PDTC with DTC, and 3 also had ATC. The DTC component on these 15 cases included follicular carcinoma FTC (7), follicular variant of papillary carcinoma FVPC (6) and papillary thyroid carcinoma PTC (2). In addition 6 cases were pure PDTC and 2 pure ATC. Seventeen cases of DTC (9 FTC, and 8 PTC) only were also selected from the same period. Sections were deparaffinized and individual tumor areas were retrieved by laser capture microdissection. Total RNA was isolated using the RecoverAll Total Nucleic Acid Isolation Kit and reverse transcribed into cDNA using miRNA-specific stem-looped primers and preamplified. miRNA profiling was done by qRT-PCR with the TaqMan Human MicroRNA A Array v2.0. Data analysis was done using Statminer and MeV software.
Results: Unsupervised hierarchical clustering analysis revealed that FTC and PDC tend to cluster together in the absence of ATC, with few differentially expressed miRNAs e.g. miR-891a. Consequently, ATC has a distinct miRNA signature significantly different from FTC and PDTC (which cluster together). Interestingly, in samples with evidence of all components i.e. FTC, PDTC and ATC, miRNA expression is very similar within individual components. Similar observations were made for PTC. However, FVPC has a distinct miRNA signature as compared to PDTC (c.f. FTC).
Conclusions: We present some interesting data generated from preliminary analysis of miRNA expression profile, especially with respect to PDTC. In tumors with all three components (i.e. DTC, PDTC and ATC), the expression profiles tend to be similar indicating a fundamental miRNA programming change at the level of DTC putting it at an increased risk for ATC. Several miRNAs were found to be differentially expressed between the two major groups (FTC and PDTC without ATC) and (FTC and PDTC with ATC) and will be validated by miRNA-specific qRT-PCR.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 80, Monday Morning