Prognostic value of N-myc immunoreactivity in medullary thyroid carcinoma

Background. The analysis of N-myc expression in some neuroendocrine tumors has been reported to provide prognostic information. To the authors' knowledge, no attempts have been made thus far to correlate N-myc expression with the clinical outcome of medullary thyroid carcinoma (MTC). Methods. N- myc gene product immunoreactivity was evaluated in 34 patients with MTC with long term follow-up, using the OA-11-803 polyclonal antiserum. The results were related to patient age and sex, sporadic or familial disease, tumor size, stage, growth rate (as determined by proliferating cell nuclear antigen [PCNA] immunostaining), and to clinical outcome. Results. Patients harboring tumors with greater than 10% neoplastic cells immunoreactive to the N-myc antiserum (58% of the cases investigated) had significantly greater tumor size (P = 0.031) than patients with fewer or no N-myc immunoreactive cells. Deregulated expression of N-myc protein in tumor cells was not due to gene amplification, as demonstrated by multiplex polymerase chain reaction (PCR). In univariate analysis, patients with more than 10% immunoreactive neoplastic cells showed a significantly shorter disease free survival than did the remaining patients (P = 0.002). Among the other clinicopathologic parameters evaluated, male sex (P = 0.039) and sporadic disease (P = 0.035) also were associated with shorter disease free survival. In multivariate analysis, N- myc immunoreactivity (P = 0.039) and male sex (p = 0.050) retained a significant correlation with poor prognosis. Conclusions. Our results suggest that immunoreactivity to the N-myc antiserum, but not tumor growth fraction as evaluated by PCNA immunostaining, is a novel and useful adjunct to predict clinical behavior of MTC.