ORIGINAL ARTICLE
Molecular profiling of sporadic medullary thyroid carcinomas – a next-generation sequencing-based study
1
Department of Pathology, Hamidiye Faculty of Medicine, University of Health Sciences, Istanbul, Turkey
2
Department of Pathology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
3
Tubitak Mam Institute of Genetic Engineering and Biotechnology, Istanbul, Turkey
4
Departmenf of Endocrin Surgery, Medical Faculty, Istinye University, Istanbul, Turkey
5
Department of Basic Medical Sciences, Hamidiye Faculty of Medicine, University of Health Sciences, Istanbul, Turkey
6
Next Generation Sequencing Laboratory, Experimental Medicine Application and Research Centre, University of Health Sciences, Istanbul, Turkey
7
Department of Medical Services and Techniques, Medical Laboratory Techniques, Hamidiye Vocational School of Health Services, University Health Sciences, Istanbul, Turkey
8
Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey
9
Department of Endocrinology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
10
Department of Basic Medical Sciences, Department of Medical Biology, Hamidiye Faculty of Medicine, University of Health Sciences, Istanbul, Turkey
11
Department of General Surgery, Çam and Sakura City Hospital, Istanbul, Turkey
12
Department of Molecular Oncology, Hamidiye Institute of Health Sciences, University of Health Sciences, Istanbul, Turkey
Submission date: 2025-06-24
Final revision date: 2025-08-14
Acceptance date: 2025-08-18
Publication date: 2025-11-28
Pol J Pathol 2025;76(3):195-213
KEYWORDS
TOPICS
ABSTRACT
Medullary thyroid carcinomas (MTCs) are 75% sporadic and 25% hereditary. This study aimed to determine the histopathological parameters and molecular changes of sporadic MTCs in a university hospital by targeted next-generation sequencing (NGS) including 62 genes. All RET mutations were missense mutations.
EIF1AX was suggested by artificial intelligence as a gene of interest for further analysis; subsequent testing revealed a pathogenic missense mutation in this gene in a patient with advanced-stage disease, who died at the 25th month of follow-up due to liver metastasis. We identified different gene mutations that could be associated with nodal metastasis in the presence or absence of RET mutation. We identified mutations that may be involved in tumour progression and have prognostic significance, such as HRAS, MAP3K1, and EIF1AX.
We observed KDR mutation in this cohort. Although driver mutations in sporadic medullary thyroid carcinoma (sMTC) mostly come from targeted NGS data in tumours from patients with localised disease, NGS findings can also be used for therapeutic purposes in advanced-stage sMTC cases with progressive local-regional or distant metastatic disease.
We believe that additional studies should be conducted with a larger number of patients so that the findings can be included in the treatment guidelines to be prepared.
EIF1AX was suggested by artificial intelligence as a gene of interest for further analysis; subsequent testing revealed a pathogenic missense mutation in this gene in a patient with advanced-stage disease, who died at the 25th month of follow-up due to liver metastasis. We identified different gene mutations that could be associated with nodal metastasis in the presence or absence of RET mutation. We identified mutations that may be involved in tumour progression and have prognostic significance, such as HRAS, MAP3K1, and EIF1AX.
We observed KDR mutation in this cohort. Although driver mutations in sporadic medullary thyroid carcinoma (sMTC) mostly come from targeted NGS data in tumours from patients with localised disease, NGS findings can also be used for therapeutic purposes in advanced-stage sMTC cases with progressive local-regional or distant metastatic disease.
We believe that additional studies should be conducted with a larger number of patients so that the findings can be included in the treatment guidelines to be prepared.
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