[1829] Structural and Functional High-Throughput Genome Analysis Helps Differential Diagnosis between Follicular Adenomas and Carcinomas: Results in a Series of 62 Patients

Philippe Vielh, Catherine Richon, Guillaume Meurice, Bastien Job, Zsofia Balogh, Alexander Valent, Ludovic Lacroix, Virginie Marty, Nelly Motte, Philippe Dessen, Bernard Caillou, Abir Al Ghuzlan, Jean-Michel Bidart, Vladimir Lazar, Adel K El-Naggar, Martin Schlumberger. Institut Gustave Roussy, Villejuif, France; MD Anderson Cancer Center, Houston, TX

Background: Although fine needle aspiration (FNA) cytology is an efficient method for diagnosing the benign or malignant nature of thyroid nodules, distinction between follicular adenomas (FA) and follicular carcinomas (FC) may still represent a difficult task. Identification of distinct structural and functional genomic alterations between these two groups of tumors, potentially applicable to cytological specimens, would be therefore of major interest. Our previous array comparative genomic hybridization (aCGH) results showed that by testing 3 chromosomal abnormalities 50% of the carcinomas can be identified (USCAP 2011, [1208]). In this study, genomic aberrations detected by fluorescent in situ hybridization (FISH) and transcriptomic profile assessed by microarray are studied in a series of frozen samples from histologically proven FA and FC.
Design: A large set of molecular abnormalities in a cohort of 62 patients (see table) were analyzed by molecular methods. All samples underwent FISH analysis using commercially available probes specific to the 3 already described chromosomal anomalies on touch preparations of the corresponding tumors to define aberrant status. Samples with good RNA quality were further hybridized on Agilent 8x60K microarrays (AMADID 28004) to obtain their transcriptomic profile.

The cohort of follicular carcinomas (FC) and follicular adenomas (FA) of the thyroid.
Chromosomal Abnormalities Detected*FC**FA**Total**
Yes18 (13)0 (0)18 (13)
No18 (10)26 (17)44 (27)
Total36 (23)26 (17)62 (40)
*Chromosomal abnormalities were tested by FISH. **The number of samples on which gene expression profiling were performed is in brackets.

Results: The class comparison of transcriptomic profile between FA and FC not having chromosomal abnormalities raised a list of 242 transcripts. These transcripts classified all of the profiles in two groups: one composed of 13 adenomas, the other composed of 10 carcinomas and 4 adenomas known to be mutated in either KRAS, HRAS or NRAS genes (data not shown).
Conclusions: In the group of follicular lesions without chromosome alteration detected by FISH, gene expression profiling is able to further differentiate adenomas from carcinomas. These preliminary results should now be validated on an independent series.
Category: Special Category - Pan-genomic/Pan-proteomic approaches to Cancer

Tuesday, March 5, 2013 9:30 AM

Poster Session III # 226, Tuesday Morning


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