The Increase in Papillary Thyroid Cancer Incidence in the U.S. during the Last Four Decades Is Accompanied by a High and Stable Frequency of BRAF Mutations and a Sharp Increase in NRAS Mutations
Chan K Jung, Jay H Lubin, Alina V Brenner, Mark P Little, Alice J Sigurdson, Yuri E Nikiforov. University of Pittsburgh, Pittsburgh; The Catholic University of Korea, Seoul, Republic of Korea; National Institute of Health, Bethesda
Background: The incidence of thyroid cancer in the U.S. has been steadily increasing over the last 40 years, primarily due to the tripling of papillary thyroid carcinoma (PTC) based on Surveillance, Epidemiology, and End Results (SEER) data. However, changes in histopathology and molecular genetics of PTC over this time have not been well studied.
Design: We examined demographic, pathologic and molecular changes in PTC over the past 35 years in 469 cases from one institution. Consecutive PTC cases were studied during four pre-selected periods: 1974-85 (n=127), 1990-92 (n=59), 2000 (n=53), and 2009 (n=230). Histological glass slides were reviewed, and molecular analyses for BRAF mutation and three RAS mutations (KRAS, NRAS, HRAS) were performed on 361 tumors of ≥3 mm in size.
Results: Mean age at diagnosis of PTC cases increased over time from 38 to 51.5 years (ptrend<10-12), agreeing with SEER data. The proportion of microcarcinomas (≤ 1cm) increased from 33% to 51% (ptrend=0.001). The prevalence of extrathyroidal extension and lymph node metastasis decreased from 40% to 21% (ptrend=0.0002) and from 27% to 18% (ptrend=0.04), respectively. The proportion of all tumors with classic papillary growth pattern decreased (76% to 36%; ptrend<10-12), whereas tumors with a follicular pattern increased (18% to 57%; ptrend<10-12). Surprisingly, the prevalence of BRAF mutation was stable: 43% in 1974-85 and 41% in 2009. The prevalence of BRAF mutation increased in classic papillary variant (53% to 76%; ptrend=0.04), and showed a trend for increase in the follicular variant (0% to 10%; ptrend=0.09). The proportion of RAS mutations increased from 7% to 25% (ptrend=0.00001), exclusively due to NRAS mutations that occurred in tumors with the follicular variant histology.
Conclusions: Our results suggest that the increase in incidence of PTC over the last four decades was characterized by increased age at diagnosis and detection of smaller-sized, intrathyroidal PTC, and tumors with the follicular growth pattern. However, the increase coincided with a stably high frequency of BRAF mutation, arguing against the notion that it is due to detection of clinically irrelevant, non-progressing tumors.
Monday, March 19, 2012 2:15 PM
Platform Session: Section H, Monday Afternoon