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Prognostic markers and response to vandetanib therapy in sporadic medullary thyroid cancer patients.

Abstract：

OBJECTIVE:Medullary thyroid carcinoma (MTC) occurs sporadically in 75% of patients. Metastatic disease is associated with significantly poorer survival. The aim of this study was to identify prognostic markers for progressive MTC and oncogenic factors associated with response to vandetanib therapy. DESIGN AND METHODS:Clinical courses of 32 patients with sporadic MTC (n=10 pN0cM0, n=8 pN1cM0, n=14 pN1cM1) were compared with genetic profiles of the patients' primary tumour tissue. Analysis for RET proto-oncogene mutations was performed by Sanger sequencing and next-generation sequencing (NGS). The mRNA expression (mRNA count) of 33 targets was measured by nCounter NanoString analysis. RESULTS:Somatic RET mutations occurred in 21/32 patients. The RET918 mutation was found in 8/14 pN1cM1 patients. BRAF (P=0.019), FGFR2 (P=0.007), FGFR3 (P=0.044) and VEGFC (P=0.042) mRNA expression was significantly lower in pN1cM0/pN1cM1 compared with pN0cM0 patients, whereas PDGFRA (P=0.026) mRNA expression was significantly higher in pN1cM0/pN1cM1 when compared with pN0cM0 patients. Among the 10/32 vandetanib-treated patients, 5 showed partial response (PR), all harbouring the RET918 mutation. mRNA expression of FLT1 (P=0.039), FLT4 (P=0.025) and VEGFB (P=0.042) was significantly higher in therapy responders. CONCLUSIONS:In this study, we identified molecular markers in primary tumour tissue of sporadic MTC associated with the development of metastasis (both lymph node and organ metastasis) as well as response to vandetanib therapy.

journal_name

Eur J Endocrinol

journal_title

European journal of endocrinology

authors

Tiedje V,Ting S,Walter RF,Herold T,Worm K,Badziong J,Zwanziger D,Schmid KW,Führer D

doi

10.1530/EJE-16-0252

subject

Has Abstract

pub_date

2016-09-01 00:00:00

pages

173-80

issue

3

eissn

0804-4643

issn

1479-683X

pii

EJE-16-0252

journal_volume

175

pub_type

杂志文章

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