Prognostic factors in medullary thyroid carcinoma: evaluation of 741 patients from the German Medullary Thyroid Carcinoma Register

Abstract

A retrospective study of 741 patients with medullary thyroid carcinoma diagnosed between 1967 and 1991 was carried out by members of the German Medullary Thyroid Carcinoma Study Group to evaluate prognostic factors. A total of 559 patients (75%) were considered to have sporadic disease, and 182 (25%) had the familial type. The sex ratio (male to female) was 1:1.4 in sporadic disease patients, and the mean age at diagnosis was 45.9 years (range 5-81 years). For familial disease patients the sex ratio was 1:1.1, and the mean age at diagnosis was 33.4 (range 5-77 years). The follow-up time for 630 patients ranged from 1 month to 20.8 years (mean 13.0 years). The overall adjusted survival rate was 86.7% at 5 years and 64.2% at 10 years. In a univariate analysis the stage of disease at diagnosis, age, sex, and type of disease (sporadic, familial) were relevant prognostic factors, with a better prognosis for young female patients with familial disease and diagnosed at an early stage. In a multivariate proportional hazards analysis, the difference in the survival rate of patients with familial disease versus those with the sporadic form disappeared, while prognostic information provided by age and sex was still significant. The poorer prognosis of patients with sporadic medullary thyroid carcinoma may be related to the patients' older age at detection and more advanced tumor stage at diagnosis. There seems to be no difference in biological behavior between tumors of the sporadic and those of the familial type.

Medullary Thyroid Carcinoma: Nationwide Japanese Survey of 634 Cases in 1996 and 271 Cases in 2002

“…The reason for this discrepancy is unclear and may due to racial or environmental factors. MEN2A was the most common hereditary disorder, and was followed by FMTC and MEN2B, consistent with results reported previously [8][9][10]. The male-to-female ratios of both the hereditary and sporadic forms decreased between the 1996 survey and the 2002 survey, but the reason for this change is also unclear.…”

“…This is thought to have been the result of rapid and early detection of mutations in the RET proto-oncogene, and it is particularly important because diagnosis at a later age is associated with a poorer outcome. Some authors have stated that a better outcome is more likely if MTC is detected below the age of 40 years [8,9]. The age of the MEN2B patients did not decrease, and the reason for this is thought to be the small numbers of MEN2B patients.…”

Pathogenesis, diagnosis and management of thyroid nodules in children

“…The hereditary forms of thyroid carcinoma are less frequent than the sporadic type and are mainly related to medullary thyroid carcinoma (MTC) of C-cell origin (25% of MTC cases are hereditary vs 75% sporadic) (Raue et al 1993, Eng 2000. We should consider such a risk in a child if one of the parents is affected by MTC and carries the germ-line mutation within a ret protooncogene.…”

Over-representation of a germline RET sequence variant in patients with sporadic medullary thyroid carcinoma and somatic RET codon 918 mutation

“…About 75% of all MTCs are believed to be sporadic (Bergholm et al, 1990;Raue et al, 1993), and the remaining 25% comprise the autosomal dominant multiple endocrine neoplasia type 2 (MEN 2) syndromes, MEN 2A, MEN 2B and familial MTC (Farndon et al, 1986;Schimke, 1984). Germline mutations of the RET protooncogene a ecting exons 10, 11, 13, 14, 15 and 16 have been found to be associated with MEN 2 (Bolino et al, 1995;Carlson et al, 1994;Donis-Keller et al, 1993;Eng et al, 1994Eng et al, , 1995Farndon et al, 1986;Gimm et al, 1997;Hofstra et al, 1994;Mulligan et al, 1993;Schimke, 1984; Smith et al, 1997).…”