Molecular Characterization of 61 Cases of Follicular Adenomas and Carcinomas of the Thyroid
Philippe Vielh, Catherine Richon, Guillaume Meurice, Bastien Job, Ludovic Lacroix, Virginie Marthy, Nelly Motte, Alexander Valent, Bernard Caillou, Abir Al Ghuzlan, Jean-Michel Bidart, Adel El Naggar, Vladimir Lazar, Philippe Dessen, Martin Schlumberger. Institut Gustave Roussy, Villejuif, France; MD Anderson Cancer Center, Houston
Background: Although fine needle aspiration cytology (FNAC) is an efficient method for diagnosing the benign or malignant nature of thyroid nodules, distinction between follicular adenomas and carcinomas may still represent a difficult task. Identification of distinct genomic alterations between these two groups of tumors, potentially applicable to cytological specimens, should be therefore of major interest.
Design: A series of 61 cases consisting of 31 cases of follicular adenomas and of 30 cases of follicular carcinomas were characterized by molecular methods: mutations in the RAS (H, K and N), BRAF, CTNNB1 and PIK3CA genes were assessed by sequencing, PAX8/PPARg and RET/PTC1 translocations by RT-PCR, and microRNA (miRNA) expression using 8x15K microarrays.
Results: Out of the 61 patients, 35 were female and 26 were male with a median age of 59 (21 to 86) and 58 (28 to 83) years, respectively. Median size of follicular adenomas was 3 (1 to 5.5) cm and histological subtypes were microfollicular in 6 (19%) cases, macrofollicular in 9 (29%) cases and of mixed subtype in 16 (52%) cases. Mean size of follicular carcinomas was 3.7 (1 to 15) cm and subtypes were microinvasive in 18 (60%) cases and widely invasive in 12 (40%) cases. Mutations (n=1) and translocations (n=0) were rarely found in adenomas as compared with follicular carcinomas (n=11 and n=3, respectively).
After data processing, 281 miRNA were validated for further analysis. An unsupervised clustering of 57 tumor samples (adenomas and carcinomas) shows two well distinct clusters: the first one covers 26 out of 28 carcinomas (93%) whereas the second one covers 28 out of 29 adenomas (97%). The differential analysis of carcinomas versus adenomas raised 20 miRNA: 19 were over-expressed in carcinomas, and one in adenoma. Further analysis of these 20 miRNA allows us to identify a signature composed of 10 miRNAsdistinguishing adenomas from carcinomas.
Conclusions: In conclusion, follicular lesions of the thyroid are clearly differentiated by the study of a small subset of miRNAs. Further studies are needed to verify these data before being used as an adjunct for helping the differential diagnosis between follicular adenomas and follicular carcinoma on cytological material obtained by FNAC, and to explore their functional significance.
Category: Head & Neck
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 175, Tuesday Afternoon