Outcome of Patients with Different MEN2A Germline Mutations

Abstract

Objectives:

Medullary thyroid carcinoma (MTC) behavior in MEN2 present variations, ranging from indolent MTC, in patients harboring intra-cellular “weak mutations, to highly aggressive disease, with RET mutation in codons 634 or 918. We compared the outcomes among patients with different germline mutations.

Methods:

Retrospective chart review. Between January 2002 and December 2011, 67 MTC patients were operated at our institution: 26 (38.8%) sporadic and 41 (61.2%) carriers of MEN2A germline RET mutations. All patients were tested for RET hot spot mutations (exons 5, 8, 10, 11, 13, 16), pre- and postoperative calcitonin (Ct), carcinoembryonic antigen (CEA), parathyroid hormone, and calcium. They were also submitted to imaging studies (ultrasound, MRI, CT and scintigraphy). Follow-up varied from 1 to 65 months (average 10.9 months). Patients were classified as cured when serum Ct concentration <2pg/mL in the last evaluation (Group A). Patients not cured were divided in two groups: Group B) Ct >2pg/mL and >40pg/mL and Group C) Ct>40pg/mL.

Results:

Nineteen patients (46.3%) were cured, most of them treated by prophylactic surgery. There was no difference according to the RET mutation. Preoperative calcitonin level ranged from 4.5 to 1367pg/mL (average 124.5) in group A from 9 to 180149 (average 124.5) in group B and from 98 to 8358 (average 2587) in group C. Fifteen patients (36.6%) presented postoperative hypoparathyroidism, not related to cure, although related to extended surgery. Younger patients who underwent prophylactic surgery had better prognosis (P = 0.02).

Conclusions:

Genetic test is the most important exam to perform in MTC patients. Outcome was better in younger patients treated by prophylactic surgery.