Norepinephrine transporter and vesicular monoamine transporter 2 tumor expression as a predictor of response to
131I-MIBG
biomarker
neuroblastoma
norepinephrine transporter
vesicular monoamine transporter 2
Journal
Pediatric blood & cancer
ISSN: 1545-5017
Titre abrégé: Pediatr Blood Cancer
Pays: United States
ID NLM: 101186624
Informations de publication
Date de publication:
Jan 2024
Jan 2024
Historique:
revised:
06
10
2023
received:
19
08
2023
accepted:
14
10
2023
medline:
27
11
2023
pubmed:
27
10
2023
entrez:
27
10
2023
Statut:
ppublish
Résumé
Prior studies suggest that norepinephrine transporter (NET) and vesicular monoamine transporter 2 (VMAT2) mediate meta-iodobenzylguanidine (MIBG) uptake and retention in neuroblastoma tumors. We evaluated the relationship between NET and VMAT2 tumor expression and clinical response to Immunohistochemistry (IHC) was used to evaluate NET and VMAT2 protein expression levels on archival tumor samples (obtained at diagnosis or relapse) from patients with relapsed or refractory neuroblastoma treated with Tumor samples and clinical data were available for 106 patients, of whom 28.3% had partial response (PR) or higher. NET H-score was not significantly associated with response (≥PR), though the percentage of tumor cells expressing NET was lower among responders (median 80% for ≥PR vs. 90% for <PR; p = .0014). VMAT2 H-score was not significantly associated with PR or higher versus less than PR, though patients with PR or higher had lower VMAT2 staining intensity (p = .005). VMAT2 H-score was significantly lower in patients with complete response (median 40 vs. 210 for patients with <complete response; p = .0049). VMAT2 H-scores were significantly higher in ganglioneuroblastoma (vs. neuroblastoma; p = .037), differentiated/poorly differentiated tumors (vs. undifferentiated; p = .0047), and tumors lacking MYCN amplification (vs. MYCN amplified; p = .0011). Markers of lower NET and VMAT2 protein expression are associated with higher likelihood of response to
Sections du résumé
BACKGROUND
BACKGROUND
Prior studies suggest that norepinephrine transporter (NET) and vesicular monoamine transporter 2 (VMAT2) mediate meta-iodobenzylguanidine (MIBG) uptake and retention in neuroblastoma tumors. We evaluated the relationship between NET and VMAT2 tumor expression and clinical response to
METHODS
METHODS
Immunohistochemistry (IHC) was used to evaluate NET and VMAT2 protein expression levels on archival tumor samples (obtained at diagnosis or relapse) from patients with relapsed or refractory neuroblastoma treated with
RESULTS
RESULTS
Tumor samples and clinical data were available for 106 patients, of whom 28.3% had partial response (PR) or higher. NET H-score was not significantly associated with response (≥PR), though the percentage of tumor cells expressing NET was lower among responders (median 80% for ≥PR vs. 90% for <PR; p = .0014). VMAT2 H-score was not significantly associated with PR or higher versus less than PR, though patients with PR or higher had lower VMAT2 staining intensity (p = .005). VMAT2 H-score was significantly lower in patients with complete response (median 40 vs. 210 for patients with <complete response; p = .0049). VMAT2 H-scores were significantly higher in ganglioneuroblastoma (vs. neuroblastoma; p = .037), differentiated/poorly differentiated tumors (vs. undifferentiated; p = .0047), and tumors lacking MYCN amplification (vs. MYCN amplified; p = .0011).
CONCLUSIONS
CONCLUSIONS
Markers of lower NET and VMAT2 protein expression are associated with higher likelihood of response to
Substances chimiques
3-Iodobenzylguanidine
35MRW7B4AD
Norepinephrine Plasma Membrane Transport Proteins
0
Vesicular Monoamine Transport Proteins
0
Radiopharmaceuticals
0
N-Myc Proto-Oncogene Protein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e30743Subventions
Organisme : NIH HHS
ID : R01 CA172067
Pays : United States
Organisme : NIH HHS
ID : R35 CA220500
Pays : United States
Informations de copyright
© 2023 Wiley Periodicals LLC.
Références
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