Prognostic value of codon 918 (ATG -> ACG) RET proto-oncogene mutations insporadic medullary thyroid carcinoma

We have determined the frequency of 918 RET protooncogene mutations (ATG->A CG) in primary MTC tumors and metastases and correlated the presence or abs ence of this mutation with the clinical outcome of patients suffering from sporadic medullary thyroid carcinoma (MTC), A total of 197 samples, consist ing of both primary tumors and lymph node metastases from 34 patients with sporadic MTC, were collected for PCR analysis of the RET 918 mutation. In 7 5 of the samples (38%), codon 918 (ATG->ACG) mutations could be detected, T he mutations showed a heterogeneous distribution: 21/34 patients (62%) had mutations in at least I tumor sample, and in 13 patients (38%) the mutation was present in all examined samples. Patients were considered 918mt when a t least I tumor sample showed the PET 918 mutation. These 918mt and 918 wil d-type (918wt) patients did not differ significantly concerning sex, age at diagnosis, TNM stage at diagnosis, number of examined tumor samples or fol low-up time. However, 918mt patients showed more aggressive development of distant metastases during follow-up (p = 0.032, Fisher's exact test) with d ecreased metastases-free survival (p < 0.005, log-rank test). Furthermore, 918mt patients had a significantly lower survival rate than 918wt patients (p = 0.048, log-rank test). These data show that the PET codon 918 mutation has a prognostic impact on patients with sporadic MTC which may influence follow-up treatment. (C) 2001 Wiley-Liss, Inc.