Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP35-Neoplasia of Endocrine Tissues
Bench to Bedside
Monday, June 17, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 10:45 AM
Room 122 (Moscone Center)

Poster Board MON-294
Nuria Valdés*1, Paloma Portillo2, Javier Tébar2, Elena Navarro3, Lluís Forga4, Anna Casterás5, Jordi Mesa6, Sonia Gaztambide7, Luis Castano8, Maria Galiana Rodriguez9 and Cristina Lamas10
1Hospital Central de Asturias, Spain, 2Hospital Virgen de la Arrixaca, 3Hospital Virgen del Rocío, 4Complejo Hospitalario de Navarra, 5Cutat Univ Vall D'Hebron,, 6Cutat Univ Vall D'Hebron, Sant Cugat Del Valle, Spain, 7Hospital de Cruces, Baracaldo Vizcaya, Spain, 8Hosp de Cruces, Baracaldo Vizcaya, Spain, 9Hospital Central de Asturias, 10Complejo Hospitalario de Albacete, Madrid, Spain
INTRODUCTION:Some studies have suggested that patients with Cys634Arg (C634R) RET mutation could have different clinical risk profile that patients with other single nucleotide exchange in codon 634 of RET proto-oncogen.

OBJECTIVE:To study clinical differences between individuals carrying C634R mutation and individuals carrying Cys634Tyr (C634Y).

METHODS:The Spanish Group for the Study of MEN designed an online national database, which was launched on January 2009. We collected data from January 2009 to December 2011 from patients carrying RET-proto-oncogen mutation in codon 634.

RESULTS:There were data on 233 patients belonging to 84 unrelated kindreds.89% of families harboured a mutation in codon 634 of RET proto-oncogen:172 patients from 63 families carried C634Y gene mutation (G1),25 patients from 9 families had C634R mutation (G2), and only 3 patients had Cys634Ser (these were excluded for the study).The mean age at the diagnosis of MEN 2A was 29.4±18.1 (0.5-75) vs 18.0±13.3 (1.4-44) years (P=0.001) in G1 and G2, respectively.C-cell hyperplasia was present in 25 patients in G1 at a mean age of 8.4±5.5 years, and in 2 patients in G2 at 1.4 and 2 years of age. Medullary thyroid cancer (MTC) was diagnosed in 83.7% patients in G1 and in 92% patients in G2. Age-related penetrance was 46% by age 30 and 85% by age 50 in G1 patients and 82% by age 30 and 100% by age 50 in G2 patients (P=0.0001). At the moment of diagnosis metastatic disease was present in 18% and 24% of patients in G1 and G2, respectively. Kaplan-Meier estimates of cumulative lymph node and distant metastases rates demonstrated that these events occurred earlier in individuals with C634R mutation (P=0.045). Pheochromocytoma (PHEO) was present in 40.6% patients in G1 and 60% patients in G2 (mean age of 40.8±15.2 vs 34.2±17.1). Age-related penetrance was 27% and 58% by age 30 in G1 and G2, respectively (P=0.012), and reached 80% in G1 and 85% in G2 by age 50.All PHEOs were diagnosed after MTC at a mean interval of 3.9±5.3 years in G1 patients and 9.6±7.9 years in G2 patients (P=0.027). Hyperparathyroidism (HPT) was present in 2.3% vs 20% (P=0.002) at a mean age of 40.1±34.6 (18-73) vs 32.5±14.9 (17.7-54.5) years (P=0.000) in G1 and G2 patients, respectively.

CONCLUSIONS:This study suggests that individuals with Cys634Arg mutation could develop MTC and metastatic disease at a younger age than individuals carrying Cys634Tyr mutation, and they could have more risk of developing HPT.

Nothing to Disclose: NV, PP, JT, EN, LF, AC, JM, SG, LC, MGR, CL

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Previous Abstract | Next Abstract >>