Search Results

You are looking at 1 - 1 of 1 items for

  • Author: Leda Sarika x
Clear All Modify Search
Open access

Katerina Saltiki, Elli Anagnostou, George Simeakis, Sofia Kouki, Anastasia Angelopoulou, Leda Sarika, Alexandra Papathoma and Maria Alevizaki


High prevalence of RET p.Gly533Cys (c.1597G > T) has been found in familial MTC in Greece (exon 8 fMTC). We studied their origin and compared clinical characteristics with non-exon 8 fMTC.


102 fMTC (FMTC and MEN2A) patients (31.4% males) were followed for 2.9–37 years (median 6 years). Fifty-one carried the RET exon 8 mutation; the remaining were non-exon 8 fMTC (exons 10, 11, 13, 14). Pre-, post-operative calcitonin, disease extent at diagnosis and follow-up and families’ place of origin were recorded.


Exon 8 fMTC were older (42.3 ± 13.3 vs 30.8 ± 17.8 years, P < 0.001), including index cases (P = 0.016). In index cases, the stage at diagnosis was more favorable in exon 8 fMTC compared to non-exon 8 fMTC (stage I and II: 65% vs 23.8%, stage III: 25% vs 57.1%, stage IV: 10% vs 19%, P = 0.025). More favorable outcome was noted in exon 8 fMTCs (remission: 72.5% vs 45.8%, stable disease: 27.5% vs 41.7%, progression: 0.0% vs 12.5%, P = 0.001). Exon 8 fMTC patients carried more frequently a second malignancy (25.5% vs 6.3%, P = 0.009); 69% of these were PTCs. Exon 8 fMTC patients were significantly older at diagnosis compared to non-exon 8 moderate-risk RET carriers and presented more favorable clinical outcome (remission: 72.5% vs 50%, stable disease: 27.5% vs 41.7%, progression: 0.0% vs 8.3%, P = 0.021). This difference remained when only index cases were analyzed. ‘Hot spots’ in the origin of exon 8 fMTCs families were recognized. No phenotype or outcome differences were found between the exon 8 families from the various regions.


In exon 8 fMTCs’ older age, favorable disease stage at diagnosis and favorable outcome suggest slow disease progression compared to non-exon 8 fMTC. Compared with moderate-risk RET mutation carriers, exon 8 fMTC patients have a more favorable clinical outcome. The higher prevalence of second malignancies, especially PTC, not previously reported, merits further investigation. Increased awareness for inherited disease is required for patients with apparently sporadic MTC originating from recognized ‘hot spots’, as the age at presentation is usually delayed.