High-Throughput Analysis of 79 Cases of Follicular Tumors of the Thyroid.
Philippe Vielh, Catherine Richon, Alexander Valent, Ludovic Lacroix, Bastien Job, Virginie Marty, Nelly Motte, Philippe Dessen, Bernard Caillou, Abir Al Ghuzlan, Jean-Michel Bidart, Vladimir Lazar, Adel K El Naggar, Martin Schlumberger. Intitut de Cancérologie Gustave Roussy, Villejuif, France; MDACC, Houston
Background: Although fine needle aspiration cytology (FNAC) is a very efficient method for diagnosing thyroid nodules, distinction between follicular adenomas and carcinomas may still represent a challenge. Identification of distinct genomic alterations between these two entities, potentially applicable to FNAC specimens by fluorescent in situ hybridization (FISH), would be therefore of major interest.
Design: We have studied 79 surgically excised and histologically verified frozen thyroid samples consisting of 33 cases of follicular adenomas and 46 cases of follicular carcinomas by comparative genomic hybridization (aCGH) on 244K arrays.
Results: Of the 79 patients, 44 were female and 35 were male with a median age of 56 (21-46) and 58 (28-87) years, respectively. Mean size of follicular adenomas was 3 (1-6.4) cm and histological subtypes were microfollicular in 7 (21%) cases, macrofollicular in 8 (24%) cases and mixed subtype in 18 (55%) cases. Mean size of follicular carcinomas was 3.7 (1-15) cm and histological subtypes were microinvasive in 28 (61%) cases and widely invasive in 18 (39%) cases. Differential analysis on the respective aCGH profiles by T-test showed that 89 differential aberrant regions were observed at a p-value threshold of 0.005 between carcinomas and adenomas, including the following genes of interest: MAGEA clusters, CDK16, FGF13, among others. aCGH also disclosed 3 different large-scale genomic abnormalities which were only specifically observed in a subpopulation of follicular carcinomas : gain of chrX (11 cases, 24%), loss of chr22 (11 cases, 24%) and loss of chr1p (8 cases, 17%). In most cases, these abnormalities were mutually exclusive, giving an overall coverage of 52% of carcinomas. Further analysis refined the identification of carcinomas specific subregions : loss on 1p35.3 (10 cases, 22%), specifically targeting the tumor suppressor gene EPB41, loss on 22q11.23 (16 cases, 35%), and gain on Xq28 (15 cases, 33%), containing a MAGEA cluster and the CETN2 gene involved in cell cycle and nucleotide excision repair pathways. Combination of these 3 subregions allowed the identification of 29 out of the 46 carcinomas (63%). In addition, anomalies of distinct chromosomal regions were significantly associated with metastatic status and overall survival.
Conclusions: We have identified a series of genomic abnormalities of diagnostic and prognostic interest and potentially applicable using FISH on FNAC material from thyroid samples.
Category: Head & Neck
Tuesday, March 1, 2011 9:00 AM
Platform Session: Section G, Tuesday Morning