Molecular Genotyping of Papillary Thyroid Carcinoma Follicular Variant According to Its Histologic Subtypes (Encapsulated vs Non-Encapsulated Infiltrative) Reveals Distinct BRAF and RAS Mutation Patterns
M Rivera, J Ricarte-Filho, J Knauf, RM Tuttle, J Fagin, R Ghossein. Memorial Sloan-Kettering Cancer Center, NY
Background: Papillary thyroid carcinoma, follicular variant (FVPTC) presents usually as an encapsulated tumor and less commonly as a partially/non-encapsulated infiltrative neoplasm. The encapsulated form rarely metastasize to lymph node (LN) (5% of cases) while infiltrative FVPTC often harbors LN metastases (65% of patients) (Cancer 2006;107:1255). The molecular profile of FVPTC was shown to be close to the follicular adenoma/carcinoma (FA/FC) group of tumors with a high RAS and very low BRAF mutation rates (Am J Surg Pathol 2006;30:216). A comprehensive survey of oncogenic mutations in FVPTC according to its encapsulated and non-encapsulated forms has not been done.
Design: Paraffin tissue from 28 patients with encapsulated FVPTC and 19 with infiltrative FVPTC were subjected to mass spectrometry genotyping encompassing the most significant oncogenes in thyroid carcinomas: 111 mutations in RET, BRAF, NRAS, HRAS, KRAS, PIK3CA, AKT1, and other related genes.
Results: There was no significant age or gender difference between encapsulated and infiltrative FVPTC. Encapsulated FVPTC were larger than their infiltrative counterpart (median size:2.9 and 2 cm respectively) but this was not significant. There was no significant differences in vascular invasion between both groups. Margins were more often positive in the infiltrative FVPTC (5/19, 26%) than in the encapsulated tumors (1/28, 4%-p=0.03). Extra-thyroid extension was markedly increased in infiltrative FVPTC (10/19, 53%) compared to encapsulated tumors (1/28, 4%-p=0.0001). The LN metastatic rate was much higher in infiltrative (10/19, 53%) than in encapsulated FVPTC (2/28, 7%-p=0.001). BRAFV600E mutation were found in 5 of 19 (26%) of the infiltrative tumor and in none of the encapsulated FVPTC (p=0.007). RAS mutations were seen in 10 of 28 (36%) of the encapsulated group (5 NRAS_Q61R, 3 HRAS_Q61, 1 HRAS_G13C and 1 KRAS_Q61R) and in only 3 of 19 (16%) of infiltrative FVPTC (2 NRAS_Q61R, 1HRASG12V) (p=0.17). No other mutations were detected.
Conclusions: 1) Encapsulated FVPTC have a molecular profile similar to FA/FC (significant rate of RAS mutation and no BRAF mutations). 2) Infiltrative FVPTC have an opposite molecular profile closer to classical PTC than to FA/FC (more BRAF and less RAS mutations than encapsulated FVPTC). 3) The molecular profile of encapsulated and infiltrative FVPTC parallels their behavior (i.e metastatic LN pattern).
Monday, March 22, 2010 8:00 AM
Platform Session: Section H 1, Monday Morning