Integrative clinical and biopathology analyses to understand the clinical heterogeneity of infantile rhabdomyosarcoma: A report from the French MMT committee.
VGLL2
infants
newborns
rhabdoid tumor
rhabdomyosarcoma
spindle cell rhabdomyosarcoma
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
07
06
2019
revised:
07
10
2019
accepted:
08
10
2019
pubmed:
23
2
2020
medline:
15
5
2021
entrez:
23
2
2020
Statut:
ppublish
Résumé
Rhabdomyosarcoma (RMS) in infants is a particular entity with various clinical presentations and outcomes. To better understand the clinical heterogeneity of RMS in infants, an integrative clinical, histological, and molecular analysis was performed. From 1989 to 2015, 37 infants aged less than 6 months with a diagnosis of RMS and archival tumor materials were identified in France. Clinical data, central pathologic review, and molecular profile including RNA sequencing were analyzed. Nineteen patients (51%) had embryonal RMS (ERMS) (including three highly differentiated ERMS with PTCH deletion), eight (22%) had spindle cell RMS (SRMS) (three VGLL2-, one NTRK-, and two (B)RAF-fusions), six (16%) had alveolar RMS (ARMS) (all FOXO1- or PAX3-fusion), two had unclassified RMS, and two poorly differentiated RMS were retrospectively diagnosed as rhabdoid tumors (RT) with loss of INI1 expression. The two RT patients died of rapid disease progression. Five-year event-free (EFS) and overall survival (OS) for RMS were 62% (95%CI, 47-82) and 52% (95%CI, 37-72). Eleven patients (31%) relapsed and four (11%) had primary refractory disease (all ERMS). In univariate analysis, EFS and OS were only associated with histology subtype, with 100% survival of known fusion-positive SRMS. RNA cluster expression showed three main clusters: ARMS, ERMS, and "VGLL2-fusion" cluster, consisting of SRMS and ERMS. Biopathology findings from this study support the different prognosis of infantile RMS. New fusion-positive SRMS has a very good outcome which may allow more conservative treatment in the future.
Sections du résumé
BACKGROUND
Rhabdomyosarcoma (RMS) in infants is a particular entity with various clinical presentations and outcomes. To better understand the clinical heterogeneity of RMS in infants, an integrative clinical, histological, and molecular analysis was performed.
METHODS
From 1989 to 2015, 37 infants aged less than 6 months with a diagnosis of RMS and archival tumor materials were identified in France. Clinical data, central pathologic review, and molecular profile including RNA sequencing were analyzed.
RESULTS
Nineteen patients (51%) had embryonal RMS (ERMS) (including three highly differentiated ERMS with PTCH deletion), eight (22%) had spindle cell RMS (SRMS) (three VGLL2-, one NTRK-, and two (B)RAF-fusions), six (16%) had alveolar RMS (ARMS) (all FOXO1- or PAX3-fusion), two had unclassified RMS, and two poorly differentiated RMS were retrospectively diagnosed as rhabdoid tumors (RT) with loss of INI1 expression. The two RT patients died of rapid disease progression. Five-year event-free (EFS) and overall survival (OS) for RMS were 62% (95%CI, 47-82) and 52% (95%CI, 37-72). Eleven patients (31%) relapsed and four (11%) had primary refractory disease (all ERMS). In univariate analysis, EFS and OS were only associated with histology subtype, with 100% survival of known fusion-positive SRMS. RNA cluster expression showed three main clusters: ARMS, ERMS, and "VGLL2-fusion" cluster, consisting of SRMS and ERMS.
CONCLUSIONS
Biopathology findings from this study support the different prognosis of infantile RMS. New fusion-positive SRMS has a very good outcome which may allow more conservative treatment in the future.
Identifiants
pubmed: 32087612
doi: 10.1002/cam4.2713
pmc: PMC7163108
doi:
Substances chimiques
Biomarkers, Tumor
0
Oncogene Proteins, Fusion
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2698-2709Informations de copyright
© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Références
Cancer. 2018 May 1;124(9):1973-1981
pubmed: 29461635
J Pathol. 2013 Sep;231(1):44-52
pubmed: 23780909
Genes Chromosomes Cancer. 2013 Jun;52(6):538-50
pubmed: 23463663
J Natl Cancer Inst. 2015 Nov 12;108(1):
pubmed: 26563356
Genes Chromosomes Cancer. 2018 Dec;57(12):611-621
pubmed: 30276917
Am J Surg Pathol. 2018 Jan;42(1):28-38
pubmed: 28877062
Am J Surg Pathol. 2016 Oct;40(10):1407-16
pubmed: 27259011
J Clin Oncol. 2012 Jul 10;30(20):2457-65
pubmed: 22665534
ESMO Open. 2016 Mar 18;1(2):e000023
pubmed: 27843590
Curr Oncol Rep. 2012 Aug;14(4):320-6
pubmed: 22532264
Pediatr Blood Cancer. 2017 Aug;64(8):
pubmed: 28097808
Pathology. 2014 Feb;46(2):95-104
pubmed: 24378391
J Clin Oncol. 2010 Sep 20;28(27):4228-32
pubmed: 20713850
Am J Surg Pathol. 2016 Feb;40(2):224-35
pubmed: 26501226
J Clin Oncol. 2005 Apr 20;23(12):2618-28
pubmed: 15728225
Genes Chromosomes Cancer. 2014 Sep;53(9):779-87
pubmed: 24824843
Histopathology. 1996 Sep;29(3):247-52
pubmed: 8884353
Eur J Cancer. 2010 Sep;46(13):2449-56
pubmed: 20538453
Mod Pathol. 2016 Dec;29(12):1532-1540
pubmed: 27562493
Lancet Oncol. 2013 Dec;14(13):e609-20
pubmed: 24275134
Am J Surg Pathol. 2017 Nov;41(11):1456-1465
pubmed: 28692601
Am J Surg Pathol. 1992 Mar;16(3):229-35
pubmed: 1599014
Cancer. 2011 Aug 1;117(15):3493-501
pubmed: 21264837
Cancer Discov. 2015 Oct;5(10):1049-57
pubmed: 26216294
Cancer Med. 2020 Apr;9(8):2698-2709
pubmed: 32087612
Am J Surg Pathol. 1993 Mar;17(3):221-30
pubmed: 8434703
Cancer. 2003 May 15;97(10):2597-604
pubmed: 12733159
Lancet Oncol. 2018 Aug;19(8):1061-1071
pubmed: 29941280
Pediatr Blood Cancer. 2019 Jun;66(6):e27652
pubmed: 30762282
Med Pediatr Oncol. 1989;17(3):210-5
pubmed: 2747593
J Pathol. 2006 Jan;208(1):17-25
pubmed: 16294371
Cancer. 2016 Jan 15;122(2):249-57
pubmed: 26479420
J Pathol. 2018 May;245(1):29-40
pubmed: 29431183
J Clin Oncol. 1988 Jan;6(1):51-5
pubmed: 2826715
J Pathol. 2016 Apr;238(5):700-10
pubmed: 26863915
Int J Radiat Oncol Biol Phys. 2019 Jan 1;103(1):19-27
pubmed: 30138647
J Clin Oncol. 1987 Jan;5(1):46-54
pubmed: 3543238
Curr Opin Cardiol. 2014 Jan;29(1):103-12
pubmed: 24284979
Cancer Genet Cytogenet. 2009 May;191(1):43-5
pubmed: 19389508
J Clin Oncol. 2005 Jul 1;23(19):4363-71
pubmed: 15994146
Cancer Cell. 2016 Mar 14;29(3):379-393
pubmed: 26923874