RAS Mutation in Thyroid FNA Specimens Enhances Predictability of Malignancy in Follicular Neoplasms
NP Ohori, MN Nikiforova, RR Seethala, KE Schoedel, YE Nikiforov. UPMC-Presbyterian, Pittsburgh, PA
Background: In thyroid neoplasms, point mutations in RAS gene (NRAS, HRAS, and KRAS) most commonly occur in follicular derived neoplasms - follicular adenoma (FA), oncocytic adenoma (OA), follicular carcinoma (FC) oncocytic carcinoma (OC), and follicular variant papillary carcinoma (FVPTC) and have been associated with more aggressive behavior. The status of RAS mutation is most applicable to cases in the cytologic category of suspicious for follicular (or oncocytic) neoplasm (SFON). The objective of this study is to correlate the status of RAS mutation in SFON cases with the surgical pathology outcome.
Design: Thyroid cytology cases diagnosed as follicular (or oncocytic) lesion (FOL) were searched from our files for the months from April 2007 to March 2008. During this period, our cytology diagnosis of FOL was equivalent to the SFON category by the Bethesda 2007 thyroid cytology classification system. For these cases, samples were collected prospectively for cytologic analysis and molecular studies. The material for the molecular studies was collected directly into nucleic acid preservative solution and RAS mutational analysis was performed by the LightCycler real time PCR and post-PCR melting curve analysis. RAS mutational status was correlated with the cytology diagnosis and surgical pathology diagnosis. Fisher exact test was used for statistical analysis.
Results: RAS mutation was found in 11 cases. Surgical pathology correlation was available for all of these cases and revealed the following: FVPTC (7), OA (1), OC (1), FA (1) and nodular thyroid [NT] (1). Ten of 11 (91%) RAS mutation positive cases were neoplastic and of these 8 were malignant (73%). By comparison, 65 cases with surgical pathology correlation were identified to be negative for RAS mutation. These cases revealed the following: papillary carcinoma (12), FVPTC (4), OA (13), OC (4), FA (8), lymphocytic thyroiditis (2) and NT (22). Forty-one of 65 (63%) RAS mutation negative cases were neoplastic and of these 20 were malignant (31%). While the difference in the rate of neoplasia between the RAS positive and RAS negative groups was almost but not statistically significant (p=0.06), the difference in the rate of malignancy between the RAS positive and RAS negative groups was significant (p=0.01).
Conclusions: For cases in the cytologic category SFON, the presence of RAS mutation indicates a greater probability of malignancy. These results have the potential of refining the clinical management of patients with this cytologic diagnosis.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 41, Wednesday Afternoon