Endocrine Abstracts

Objectives: In familial MTC there is genotype-phenotype correlation. The phenotype and clinical outcome in exon8 (G533C) carriers has not been well established.

Methods: 95 patients operated for familial MTC (27.2% males) were followed for 0.9–30 years (mean 8.0, median 5.5 years). 45.3% (n=43) were exon8 carriers (exon8MTC) and the remaning were non-exon8MTCs (n=52, exons 10, 11, 13, 14, and 16). Pre-, postoperative calcitonin, extent of disease at diagnosis and at follow-up were recorded.

Results: Exon8MTC had significantly higher age at diagnosis even after when patients diagnosed after genetic-screening were excluded (43.0±11 vs 27.9±17, P<0.001). Exon8MTC were diagnosed during 2001–2013 more frequently than before 2000 (P=0.001). No difference in sex distribution was observed. No differences in lymph node invasion, capsular infiltration, multifocality, c-cell hyperplasia, and distant metastases at diagnosis were observed between groups. No difference in disease stage at diagnosis was observed between the two groups. When patients diagnosed after genetic-screening were excluded from analysis, stage at diagnosis was more favorable in exon8MTC compared to non-exon8MTC (n=51, stage I+II: 60.9 vs 38.1%, stage III: 34.8 vs 33% stage IV: 4.3 vs 28.6%, P=0.037, linear-by-linear association). Tumour size, preoperative and postoperative calcitonin levels did not differ between groups. Significantly more favorable clinical outcome was noted in the group of exon8MTC compared to non-exon8MTC (remission: 72.5 vs 52.2%, stable disease: 27.5 vs 30.4%, progression: 0.0 vs 17.6%, P=0.0037). Interestingly, a higher percentage of exon8MTC patients carried a second malignancy either at diagnosis or at follow-up (21.4 vs 6.1%, P=0.058).

Conclusions: Familial MTC due to exon8 ret mutation is frequently diagnosed in recent years in the Greek population. The age at diagnosis is higher in exon8MTC carriers compared to non-exon8MTC. The outcome of the disease is more favorable suggesting relatively slow disease progression. The higher prevalence of second malignancies has not been previously reported and merits further investigation.