Multi-center Assessment of DLL3 Expression by Immunohistochemistry in Medullary Thyroid Carcinoma
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F25%3A10506725" target="_blank" >RIV/00179906:_____/25:10506725 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11150/25:10506725
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=1KbDFh9s7M" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=1KbDFh9s7M</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s12022-025-09894-9" target="_blank" >10.1007/s12022-025-09894-9</a>
Alternative languages
Result language
angličtina
Original language name
Multi-center Assessment of DLL3 Expression by Immunohistochemistry in Medullary Thyroid Carcinoma
Original language description
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignancy accounting for 1-2% of thyroid carcinomas. As a neuroendocrine neoplasm, it shares molecular features with other aggressive neuroendocrine carcinomas, including alterations in the Myc and Notch pathways. Delta-like ligand 3 (DLL3), an inhibitory ligand of the Notch pathway and a validated therapeutic target in small cell lung carcinoma, has attracted interest as a biomarker and potential target in other neuroendocrine tumors; however, its relevance in MTC remains poorly characterized. We performed a multicenter retrospective study of 119 MTC cases resected between 2000 and 2024 across five European institutions. DLL3 immunohistochemistry was assessed on whole sections using the Ventana SP347 antibody, with expression categorized as null (< 1%), low (1-49%), or high (>= 50%). Interobserver agreement between two endocrine pathologists was substantial (weighted kappa = 0.80). DLL3 positivity (>= 1%) was observed in 89.1% of cases; 53.8% showed low and 35.3% high expression. DLL3-high expression correlated with adverse histopathological features, including larger tumor size, high-grade histology, desmoplasia, positive surgical margins, and lymph node metastases. In survival analyses, DLL3-high expression was associated with significantly shorter disease-free survival (HR 7.96, p = 0.05) and overall survival (HR 11.6, p = 0.01). Our findings indicate that DLL3 is frequently expressed in MTC and its high expression identifies tumors with aggressive pathological characteristics and poor clinical outcomes. These results support DLL3 as a potential prognostic biomarker and therapeutic target in MTC, highlighting the need for further validation and integration into clinical trials of DLL3-directed therapies.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30109 - Pathology
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Endocrine Pathology
ISSN
1046-3976
e-ISSN
1559-0097
Volume of the periodical
36
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
8
Pages from-to
49
UT code for WoS article
001631573400001
EID of the result in the Scopus database
2-s2.0-105023912419