20.500.12556/DiRROS-15585
Medullary thyroid carcinoma and associated endocrinopathies in Slovenia from 1995 to 2021
Background: Medullary thyroid cancer (MTC) is a rare endocrine tumour that is sporadic in 75% of cases and occurs as a part of inherited cancer syndromes in approximately 25% of cases. The aim of this study was to determine the frequency and type of RET pathogenic variants (PVs) in the Slovenian MTC patient population diagnosed between 1995 and 2021 and to elucidate the full range of associated endocrinopathies. Methods: A retrospective analysis of medical records of 266 MTC patients and their relatives seen in a tertiary centre between 1995 and 2021 was performed. Sequence analysis of exons 10, 11, 13, 14, 15, and 16 of the RET gene was analysed in most patients using Sanger sequencing. From 2017, the entire sequence of RET gene was analysed in most patients using targeted next-generation sequencing. Results: Germline PVs in the RET proto-oncogene were identified in 21.6% probands from 21 different MTC families. Of their tested relatives, 65% (67/103) were RET-positive and 35% (36/103) were RET-negative. PVs were detected in codon 618 and codon 634 in 28.6%, and in codon 790 in 23.8%. The RET-positive group consisted of 52 MTC patients, 13 patients with C cell hyperplasia and 2 individuals with neither. Associated endocrinopathies were diagnosed in 8/21 families: primary hyperparathyroidism (PHPT) in six families and pheochromocytoma (PHEO) in five families. In 62% of RET-positive families (13/21), no associated endocrinopathies were diagnosed. PHEO was most commonly associated with C634R (6/13) and PHPT with C634R (4/7). Hirschsprung’s disease appeared in one patient with RET PV in codon 618. Based on data from the Cancer Registry of Republic of Slovenia, only individual cases of common cancers with well understood environmental risk factors were discovered; lung cancer in 2/21 of families, papillary thyroid cancer in 3/21 of families, cutaneous melanoma in 2/21 of families, cervical cancer in 1/21 families, and lymphoma in 1/21 families. Conclusions: Analysis of prospectively collected MTC cases during a 27-year period revealed that 21.6% of Slovenian patients are RET PV carriers. Sixty-two percent of families had none of the associated endocrinopathies, confirming the thesis that FMTC is the most common presentation. This could suggest using risk-stratified management approaches when screening for PHEO and PHPT in RET PV carriers. However, more studies are needed to evaluate potential genetic risk modifiers as well as safety, improved quality of life, and medical cost reduction in the case of a patient-oriented approach.
medullary thyroid carcinoma
multiple endocrine neoplasia
primary hyperparathyroidism
medularni rak ščitnice
multipla endokrina neoplazija
primarni hipertirodizem
true
false
true
MDPI
Angleški jezik
Slovenski jezik
by Authors
Neznano
2022-09-23 03:34:30
2022-09-23 14:20:46
2022-09-24 03:44:04
0000-00-00 00:00:00
2022
0
0
Nasl. z nasl. zaslona;
Opis vira z dne 21. 7. 2022;
str. 1091-1-1091-8
no. 7
Vol. 12
2022
0000-00-00
Zaloznikova
Objavljeno
NiDoloceno
0000-00-00
0000-00-00
2022-07-21
616-07
2075-1729
10.3390/life12071091
116049923
https://www.mdpi.com/2075-1729/12/7/1091/htm
1
16be7899-3acf-11ed-bea5-001a4af901a5
https://dirros.openscience.si/Dokument.php?lang=slv&id=20610
RAZ_Milicevic_Sara_2022.pdf
RAZ_Milicevic_Sara_2022.pdf
1
4946D0D2CB52C6752679497E9AB35934
d8b49a0defaa207a6c2865c826fb0842b26088bd9f1c548e0a4822c134970c20
88c06fac-3b29-11ed-bea5-001a4af901a5
https://dirros.openscience.si/Dokument.php?lang=slv&id=20622
Onkološki inštitut Ljubljana
0
0
0