             
|
Paper 10 (1115)
MOLECULAR ANALYSIS OF MINIMALLY INVASIVE FOLLICULAR CARCINOMAS BY GENE PROFILING
Background: The diagnosis of minimally-invasive follicular thyroid carcinoma (MIFTC) is disconcerting to both surgeons and patients. While the majority of these tumors behave like follicular adenomas, some recur in the contralateral lobe or metastasize. These studies were conducted to determine if molecular profiling can enhance our understanding of minimally invasive follicular carcinomas and to perhaps offer a better classification schema.
The 26th Annual Meeting of the American
Association of Endocrine Surgeons
April 3rd- 5th,2005 - Paradisus Riviera Cancun.
Carrie C. Lubitz, Baixin Zhu and Thomas J. Fahey III
Weill-Cornell Medical College, New York.
Methods: Microarray analysis was performed on 27 follicular neoplasms. Thirteen follicular adenomas were compared with seven widely-invasive follicular carcinomas (WIFTC) to generate a list of differentially expressed genes. An unsupervised cluster analysis of the test set using this list was then performed. Next, seven MIFTCs were analyzed along with the other samples in an unsupervised cluster analysis. The MIFTCs were then compared directly against both the adenoma and widely-invasive carcinoma groups to investigate genetic similarity to either group.
Results: Follicular adenomas and widely-invasive follicular carcinomas have distinct genetic profiles, with 401 differentially expressed genes (62 > 2 fold change). Unsupervised hierarchical cluster analysis of the test set separated benign from malignant follicular neoplasms with 100% accuracy. Next, seven MIFTCs, all of which showed capsular invasion and two of which showed both capsular and vascular invasion, were added to the analysis. Six out of 7 of the MIFTCs grouped with the follicular adenomas, 4 of which created their own subgroup. Of note, the one MIFTC that grouped with the WIFTC did not have vascular invasion on pathologic review. When analyzed directly, MIFTCs had 223 differently expressed genes (10 >2 fold change) compared to adenomas and 365 (62 > 2 fold) difference from widely-invasive carcinomas.
Conclusions: Molecular profiling illustrates that the majority of MIFTCs comprise a subclass of benign follicular neoplasms, and while most MIFTCs are genetically similar to adenomas, our data suggest that others may deserve greater suspicion of malignant potential. Insight into the molecular pathogenesis of minimally invasive follicular thyroid cancer can be provided by gene profiling.