Molecular and Morphologic Characterization of Thyroid Carcinomas According to Extra-Thyroid Extension Status
M Rivera, J Ricarte-Filho, J Knauf, RM Tuttle, J Fagin, R Ghossein. Memorial Sloan-Kettering Cancer Center, NY
Background: The relationships between mutational profile, histologic subtype, extra-thyroid extension (ETE) status and their impact on survival in thyroid carcinomas (TC) have not been well characterized
Design: All cases of TC with ETE but without nodal metastases at presentation (NMP) were identified over a 20 year period and grouped into gross and microscopic ETE (METE). METE was subdivided into focal (1-2 foci of 1mm in size each) and established (>2 foci or any focus >1 mm). A group of 14 papillary thyroid carcinomas (PTC) without ETE and NMP was also analyzed. Cases with paraffin tissues were subjected to mass spectrometry genotyping encompassing the most significant oncogenes in TC: 111 mutations in RET, BRAF, NRAS, HRAS, KRAS, PIK3CA, AKT1, and other related genes.
Results: 81 (10%) of 829 patients in the database had ETE and no NMP. Histologic subtype in TC with METE (n=52) was as follows: Classical PTC- 24 (46%), Tall cell PTC- 15 (29%), PTC microcarcinoma- 7 (13%), PTC follicular variant (FV) infiltrative- 2 (4%), solid variant PTC- 1(2%), poorly differentiated TC (PDTC)- 2 (4%),anaplastic- 1(2%). In cases with gross ETE (n=29), there were 10 classical PTC (34.5%), 6 Tall cell PTC (20.7%), 1 PTC FV infiltrative (3.5%), 9 PDTC (31%), 3 anaplastic (10.3%). There was a higher disease specific survival (DSS) in patients with METE compared to those with gross ETE (p<0.0001). Except for the anaplastic case, all patients with METE did not recur including 23 without radioactive iodine therapy (median follow up 9 years). Within patients with gross ETE into trachea/esophagus, higher grade (defined by high mitotic activity and/or tumor necrosis) correlated with worse DSS (p<0.05). There was no survival difference within METE (focal vs established). 56 cases with ETE were genotyped as follows: 39 BRAFV600E (69.6%), 1 BRAFV600E-AKT1 (1.8%), 1 N-RAS (1.8%), 1 K-RAS (1.8%), 14 wild type (25%). Within PTC, BRAF positivity rate according to ETE status was as follows: 13+/15 (87%) in gross ETE, 25+/34 (73%) in METE, 5+/13 (38%) in no ETE. (No ETE vs ETE,p=0.01). If PTC FV are excluded, BRAF positivity does not correlate with ETE status in classical/tall cell PTC.
Conclusions: 1) PTC with METE without NMP recur very rarely. 2) High mitotic activity/tumor necrosis confers worse DSS even in patients stratified for gross ETE in trachea/esophagus. 3) BRAF positivity correlates with the presence of ETE in PTC but this relationship is lost within classical/tall cell PTC if PTC FV are excluded from the analysis.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 37, Tuesday Afternoon