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.
Roncalli
M
M
II Department of Pathology, University of Milan School of Medicine, Italy.
Viale
G
G
Grimelius
L
L
Johansson
H
H
Wilander
E
E
Alfano
R M
RM
Springall
D
D
Battezzati
P M
PM
Polak
J M
JM
Coggi
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D018276:Carcinoma, Medullary / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009687:Nuclear Proteins / Q000032:analysis; D016133:Polymerase Chain Reaction; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis* / Q000276:immunology; D012737:Sex Factors; D013964:Thyroid Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000276:immunology
D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D016271:Proto-Oncogene Proteins c-myc