Universität zu Köln

Asgharzadeh, Shahab ORCID: 0000-0002-0510-3848, Salo, Jill A., Ji, Lingyun, Oberthuer, Andre, Fischer, Matthias, Berthold, Frank, Hadjidaniel, Michael, Liu, Cathy Wei-Yao, Metelitsa, Leonid S., Pique-Regi, Roger ORCID: 0000-0002-1262-2275, Wakamatsu, Peter, Villablanca, Judith G., Kreissman, Susan G., Matthay, Katherine K., Shimada, Hiroyuki, London, Wendy B., Sposto, Richard and Seeger, Robert C. (2012). Clinical Significance of Tumor-Associated Inflammatory Cells in Metastatic Neuroblastoma. J. Clin. Oncol., 30 (28). S. 3525 - 3533. ALEXANDRIA: AMER SOC CLINICAL ONCOLOGY. ISSN 1527-7755

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Abstract

Purpose Children diagnosed at age >= 18 months with metastatic MYCN-nonamplified neuroblastoma (NBL-NA) are at high risk for disease relapse, whereas those diagnosed at age < 18 months are nearly always cured. In this study, we investigated the hypothesis that expression of genes related to tumor-associated inflammatory cells correlates with the observed differences in survival by age at diagnosis and contributes to a prognostic signature. Methods Tumor-associated macrophages (TAMs) in localized and metastatic neuroblastomas (n = 71) were assessed by immunohistochemistry. Expression of 44 genes representing tumor and inflammatory cells was quantified in 133 metastatic NBL-NAs to assess age-dependent expression and to develop a logistic regression model to provide low-and high-risk scores for predicting progression-free survival (PFS). Tumors from high-risk patients enrolled onto two additional studies (n = 91) served as independent validation cohorts. Results Metastatic neuroblastomas had higher infiltration of TAMs than locoregional tumors, and metastatic tumors diagnosed in patients at age >= 18 months had higher expression of inflammation-related genes than those in patients diagnosed at age < 18 months. Expression of genes representing TAMs (CD33/CD16/IL6R/IL10/FCGR3) contributed to 25% of the accuracy of a novel 14-gene tumor classification score. PFS at 5 years for children diagnosed at age > 18 months with NBL-NA with a low-versus high-risk score was 47% versus 12%, 57% versus 8%, and 50% versus 20% in three independent clinical trials, respectively. Conclusion These data suggest that interactions between tumor and inflammatory cells may contribute to the clinical metastatic neuroblastoma phenotype, improve prognostication, and reveal novel therapeutic targets. J Clin Oncol 30:3525-3532. (C) 2012 by American Society of Clinical Oncology

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Asgharzadeh, Shahab UNSPECIFIED orcid.org/0000-0002-0510-3848 UNSPECIFIED Salo, Jill A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ji, Lingyun UNSPECIFIED UNSPECIFIED UNSPECIFIED Oberthuer, Andre UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Berthold, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Hadjidaniel, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Liu, Cathy Wei-Yao UNSPECIFIED UNSPECIFIED UNSPECIFIED Metelitsa, Leonid S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pique-Regi, Roger UNSPECIFIED orcid.org/0000-0002-1262-2275 UNSPECIFIED Wakamatsu, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Villablanca, Judith G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kreissman, Susan G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Matthay, Katherine K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Shimada, Hiroyuki UNSPECIFIED UNSPECIFIED UNSPECIFIED London, Wendy B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sposto, Richard UNSPECIFIED UNSPECIFIED UNSPECIFIED Seeger, Robert C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-481554
DOI:	10.1200/JCO.2011.40.9169
Journal or Publication Title:	J. Clin. Oncol.
Volume:	30
Number:	28
Page Range:	S. 3525 - 3533
Date:	2012
Publisher:	AMER SOC CLINICAL ONCOLOGY
Place of Publication:	ALEXANDRIA
ISSN:	1527-7755
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HIGH-RISK NEUROBLASTOMA; BONE-MARROW; FAVORABLE PROGNOSIS; EXPRESSION; SURVIVAL; STAGE; CHEMOTHERAPY; MACROPHAGE; CHILDREN; ANTIBODY Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48155