The Presence of ALK Alterations and Clinical Relevance of Crizotinib Treatment in Pediatric Solid Tumors

Luca Felkai, Rita Bánusz, I. Kovalszky, Z. Sápi, M. Garami, Gergő Papp, Katalin Karászi, Edit Varga, Monika Csóka

Research output: Article

3 Citations (Scopus)

Abstract

Soft tissue sarcomas (STS) and neuroblastomas (NBL), are childhood malignancies still associated with poor prognoses despite the overall improvement in childhood tumor survival of the past decades. Anaplastic lymphoma kinase (ALK) inhibition is promising new strategy to improve the outcome of these pediatric tumors. Eighteen histologic samples of pediatric STS and 19 NBL patients were analyzed for ALK abnormalities using fluorescent in situ hybridization (FISH) with break-apart probes and immunohistochemistry (IHC). ALK alterations were presented in 20 of the 37 sections. The presence of ALK alteration in NBL samples were detected using IHC in 84,2% of all cases compared to 21,1% FISH positivity. In STS cases the results were less different (IHC 16,7% vs FISH 22,2%). The difference can be explained by the different type of molecular alterations. FISH method detected translocation and amplification, but not the point mutation of ALK gene. IHC confirmed the diagnosis by detecting the expression of ALK protein.After ALK positivity was proven, the effectiveness and safety of the crizotinib therapy was examined in 4 patients (1 alveolar rhabdomyosarcoma (RMA), 1 embryonal rhabdomyosarcoma (RME), 1 inflammatory myofibroblastic tumor (IMT), 1 NBL). We observed continuous remission of the IMT patient, all other cases the inhibitor treatment was not curative.Our findings underline the importance of screening the ALK status parallel with both IHC and FISH. Crizotinib treatment had a long-term effect in ALK positive IMT patients, however itwas only temporary efficient in relapsed, progressive STS and NBL.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalPathology and Oncology Research
DOIs
Publication statusAccepted/In press - okt. 28 2017

Fingerprint

Pediatrics
Fluorescence In Situ Hybridization
Neuroblastoma
Sarcoma
Neoplasms
Immunohistochemistry
Therapeutics
Alveolar Rhabdomyosarcoma
anaplastic lymphoma kinase
crizotinib
Point Mutation
Safety
Survival
Genes
Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Oncology
  • Cancer Research

Cite this

The Presence of ALK Alterations and Clinical Relevance of Crizotinib Treatment in Pediatric Solid Tumors. / Felkai, Luca; Bánusz, Rita; Kovalszky, I.; Sápi, Z.; Garami, M.; Papp, Gergő; Karászi, Katalin; Varga, Edit; Csóka, Monika.

In: Pathology and Oncology Research, 28.10.2017, p. 1-8.

Research output: Article

Felkai, Luca ; Bánusz, Rita ; Kovalszky, I. ; Sápi, Z. ; Garami, M. ; Papp, Gergő ; Karászi, Katalin ; Varga, Edit ; Csóka, Monika. / The Presence of ALK Alterations and Clinical Relevance of Crizotinib Treatment in Pediatric Solid Tumors. In: Pathology and Oncology Research. 2017 ; pp. 1-8.
@article{e2a32256f68d4a268a8f93da6b650dd1,
title = "The Presence of ALK Alterations and Clinical Relevance of Crizotinib Treatment in Pediatric Solid Tumors",
abstract = "Soft tissue sarcomas (STS) and neuroblastomas (NBL), are childhood malignancies still associated with poor prognoses despite the overall improvement in childhood tumor survival of the past decades. Anaplastic lymphoma kinase (ALK) inhibition is promising new strategy to improve the outcome of these pediatric tumors. Eighteen histologic samples of pediatric STS and 19 NBL patients were analyzed for ALK abnormalities using fluorescent in situ hybridization (FISH) with break-apart probes and immunohistochemistry (IHC). ALK alterations were presented in 20 of the 37 sections. The presence of ALK alteration in NBL samples were detected using IHC in 84,2{\%} of all cases compared to 21,1{\%} FISH positivity. In STS cases the results were less different (IHC 16,7{\%} vs FISH 22,2{\%}). The difference can be explained by the different type of molecular alterations. FISH method detected translocation and amplification, but not the point mutation of ALK gene. IHC confirmed the diagnosis by detecting the expression of ALK protein.After ALK positivity was proven, the effectiveness and safety of the crizotinib therapy was examined in 4 patients (1 alveolar rhabdomyosarcoma (RMA), 1 embryonal rhabdomyosarcoma (RME), 1 inflammatory myofibroblastic tumor (IMT), 1 NBL). We observed continuous remission of the IMT patient, all other cases the inhibitor treatment was not curative.Our findings underline the importance of screening the ALK status parallel with both IHC and FISH. Crizotinib treatment had a long-term effect in ALK positive IMT patients, however itwas only temporary efficient in relapsed, progressive STS and NBL.",
keywords = "ALK, Crizotinib, Inflammatory myofibroblastic tumor, Neuroblastoma, Soft tissue sarcoma",
author = "Luca Felkai and Rita B{\'a}nusz and I. Kovalszky and Z. S{\'a}pi and M. Garami and Gergő Papp and Katalin Kar{\'a}szi and Edit Varga and Monika Cs{\'o}ka",
year = "2017",
month = "10",
day = "28",
doi = "10.1007/s12253-017-0332-1",
language = "English",
pages = "1--8",
journal = "Pathology and Oncology Research",
issn = "1219-4956",
publisher = "Springer Netherlands",

}

TY - JOUR

T1 - The Presence of ALK Alterations and Clinical Relevance of Crizotinib Treatment in Pediatric Solid Tumors

AU - Felkai, Luca

AU - Bánusz, Rita

AU - Kovalszky, I.

AU - Sápi, Z.

AU - Garami, M.

AU - Papp, Gergő

AU - Karászi, Katalin

AU - Varga, Edit

AU - Csóka, Monika

PY - 2017/10/28

Y1 - 2017/10/28

N2 - Soft tissue sarcomas (STS) and neuroblastomas (NBL), are childhood malignancies still associated with poor prognoses despite the overall improvement in childhood tumor survival of the past decades. Anaplastic lymphoma kinase (ALK) inhibition is promising new strategy to improve the outcome of these pediatric tumors. Eighteen histologic samples of pediatric STS and 19 NBL patients were analyzed for ALK abnormalities using fluorescent in situ hybridization (FISH) with break-apart probes and immunohistochemistry (IHC). ALK alterations were presented in 20 of the 37 sections. The presence of ALK alteration in NBL samples were detected using IHC in 84,2% of all cases compared to 21,1% FISH positivity. In STS cases the results were less different (IHC 16,7% vs FISH 22,2%). The difference can be explained by the different type of molecular alterations. FISH method detected translocation and amplification, but not the point mutation of ALK gene. IHC confirmed the diagnosis by detecting the expression of ALK protein.After ALK positivity was proven, the effectiveness and safety of the crizotinib therapy was examined in 4 patients (1 alveolar rhabdomyosarcoma (RMA), 1 embryonal rhabdomyosarcoma (RME), 1 inflammatory myofibroblastic tumor (IMT), 1 NBL). We observed continuous remission of the IMT patient, all other cases the inhibitor treatment was not curative.Our findings underline the importance of screening the ALK status parallel with both IHC and FISH. Crizotinib treatment had a long-term effect in ALK positive IMT patients, however itwas only temporary efficient in relapsed, progressive STS and NBL.

AB - Soft tissue sarcomas (STS) and neuroblastomas (NBL), are childhood malignancies still associated with poor prognoses despite the overall improvement in childhood tumor survival of the past decades. Anaplastic lymphoma kinase (ALK) inhibition is promising new strategy to improve the outcome of these pediatric tumors. Eighteen histologic samples of pediatric STS and 19 NBL patients were analyzed for ALK abnormalities using fluorescent in situ hybridization (FISH) with break-apart probes and immunohistochemistry (IHC). ALK alterations were presented in 20 of the 37 sections. The presence of ALK alteration in NBL samples were detected using IHC in 84,2% of all cases compared to 21,1% FISH positivity. In STS cases the results were less different (IHC 16,7% vs FISH 22,2%). The difference can be explained by the different type of molecular alterations. FISH method detected translocation and amplification, but not the point mutation of ALK gene. IHC confirmed the diagnosis by detecting the expression of ALK protein.After ALK positivity was proven, the effectiveness and safety of the crizotinib therapy was examined in 4 patients (1 alveolar rhabdomyosarcoma (RMA), 1 embryonal rhabdomyosarcoma (RME), 1 inflammatory myofibroblastic tumor (IMT), 1 NBL). We observed continuous remission of the IMT patient, all other cases the inhibitor treatment was not curative.Our findings underline the importance of screening the ALK status parallel with both IHC and FISH. Crizotinib treatment had a long-term effect in ALK positive IMT patients, however itwas only temporary efficient in relapsed, progressive STS and NBL.

KW - ALK

KW - Crizotinib

KW - Inflammatory myofibroblastic tumor

KW - Neuroblastoma

KW - Soft tissue sarcoma

UR - http://www.scopus.com/inward/record.url?scp=85032364579&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85032364579&partnerID=8YFLogxK

U2 - 10.1007/s12253-017-0332-1

DO - 10.1007/s12253-017-0332-1

M3 - Article

C2 - 29081033

AN - SCOPUS:85032364579

SP - 1

EP - 8

JO - Pathology and Oncology Research

JF - Pathology and Oncology Research

SN - 1219-4956

ER -