Inflammatory myofibroblastic tumour of the urinary bladder: The role of immunoglobulin G4 and the comparison of two immunohistochemical antibodies and fluorescence in-situ hybridization for the detection of anaplastic lymphoma kinase alterations

Euna Choi, Sean R. Williamson, Rodolfo Montironi, Shaobo Zhang, Mingsheng Wang, John Eble, David Grignon, Antonio Lopez-Beltran, Muhammad Idrees, Lee Ann Baldridge, Marina Scarpelli, Carol L. Jones, Lisha Wang, Gregory T. Maclennan, Adeboye O. Osunkoya, Liang Cheng

Research output: Contribution to journalArticle

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Abstract

Aims: We examined gene rearrangement and the expression of anaplastic lymphoma kinase (ALK) in urinary bladder inflammatory myofibroblastic tumour (IMT) using fluorescence in-situ hybridization (FISH) and two immunohistochemical antibodies to ALK. We also investigated whether IMT represents an immunoglobulin (Ig)G4-related disease. Methods and results: The performance of the Dako FLEX ALK monoclonal antibody (CD246) and the Cell Signaling Technology ALK (D5F3) XP monoclonal antibody were compared. Overall, 11 of 16 tumours showed ALK expression by immunohistochemistry (69%). Ten demonstrated ALK expression with both stains and one was positive with D5F3 but not CD246 (91% correlation). The D5F3 antibody yielded a stronger staining intensity and a higher sensitivity. Nine tumours demonstrated ALK rearrangements (56%) by FISH. Three were ALK<sup>+</sup> by immunohistochemistry but negative for rearrangement by FISH, whereas one showed rearrangement by FISH but was negative by immunohistochemistry. In total, 12 tumours were positive for ALK abnormalities (75%). Using current criteria, no cases were classified as an IgG4-related disease. Conclusions: The ALK D5F3 immunohistochemical stain showed superior staining characteristics compared with ALK CD246. Discrepancies in the results between FISH and immunohistochemistry for ALK abnormalities may have causes that are multifactorial. By current criteria, IMT does not represent an IgG4-related disease.

Original languageEnglish
Pages (from-to)20-38
Number of pages19
JournalHistopathology
Volume67
Issue number1
DOIs
StatePublished - Jul 1 2015

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Fluorescence In Situ Hybridization
Immunoglobulins
Urinary Bladder
Antibodies
Neoplasms
Immunohistochemistry
anaplastic lymphoma kinase
Coloring Agents
Immunoglobulin G
Monoclonal Antibodies
Staining and Labeling
Gene Rearrangement
Technology
Gene Expression

Keywords

  • Anaplastic lymphoma kinase (ALK)
  • Carcinosarcoma
  • Fluorescence in-situ hybridization (FISH)
  • Immunohistochemistry
  • Inflammatory myofibroblastic tumour (inflammatory pseudotumour)
  • Molecular genetics
  • Neoplasia
  • Postoperative spindle cell nodule
  • Sarcoma
  • Soft tissue tumour
  • Spindle cell lesions
  • Urinary bladder

ASJC Scopus subject areas

  • Histology
  • Pathology and Forensic Medicine

Cite this

Inflammatory myofibroblastic tumour of the urinary bladder : The role of immunoglobulin G4 and the comparison of two immunohistochemical antibodies and fluorescence in-situ hybridization for the detection of anaplastic lymphoma kinase alterations. / Choi, Euna; Williamson, Sean R.; Montironi, Rodolfo; Zhang, Shaobo; Wang, Mingsheng; Eble, John; Grignon, David; Lopez-Beltran, Antonio; Idrees, Muhammad; Baldridge, Lee Ann; Scarpelli, Marina; Jones, Carol L.; Wang, Lisha; Maclennan, Gregory T.; Osunkoya, Adeboye O.; Cheng, Liang.

In: Histopathology, Vol. 67, No. 1, 01.07.2015, p. 20-38.

Research output: Contribution to journalArticle

Choi, Euna ; Williamson, Sean R. ; Montironi, Rodolfo ; Zhang, Shaobo ; Wang, Mingsheng ; Eble, John ; Grignon, David ; Lopez-Beltran, Antonio ; Idrees, Muhammad ; Baldridge, Lee Ann ; Scarpelli, Marina ; Jones, Carol L. ; Wang, Lisha ; Maclennan, Gregory T. ; Osunkoya, Adeboye O. ; Cheng, Liang. / Inflammatory myofibroblastic tumour of the urinary bladder : The role of immunoglobulin G4 and the comparison of two immunohistochemical antibodies and fluorescence in-situ hybridization for the detection of anaplastic lymphoma kinase alterations. In: Histopathology. 2015 ; Vol. 67, No. 1. pp. 20-38.
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abstract = "Aims: We examined gene rearrangement and the expression of anaplastic lymphoma kinase (ALK) in urinary bladder inflammatory myofibroblastic tumour (IMT) using fluorescence in-situ hybridization (FISH) and two immunohistochemical antibodies to ALK. We also investigated whether IMT represents an immunoglobulin (Ig)G4-related disease. Methods and results: The performance of the Dako FLEX ALK monoclonal antibody (CD246) and the Cell Signaling Technology ALK (D5F3) XP monoclonal antibody were compared. Overall, 11 of 16 tumours showed ALK expression by immunohistochemistry (69{\%}). Ten demonstrated ALK expression with both stains and one was positive with D5F3 but not CD246 (91{\%} correlation). The D5F3 antibody yielded a stronger staining intensity and a higher sensitivity. Nine tumours demonstrated ALK rearrangements (56{\%}) by FISH. Three were ALK+ by immunohistochemistry but negative for rearrangement by FISH, whereas one showed rearrangement by FISH but was negative by immunohistochemistry. In total, 12 tumours were positive for ALK abnormalities (75{\%}). Using current criteria, no cases were classified as an IgG4-related disease. Conclusions: The ALK D5F3 immunohistochemical stain showed superior staining characteristics compared with ALK CD246. Discrepancies in the results between FISH and immunohistochemistry for ALK abnormalities may have causes that are multifactorial. By current criteria, IMT does not represent an IgG4-related disease.",
keywords = "Anaplastic lymphoma kinase (ALK), Carcinosarcoma, Fluorescence in-situ hybridization (FISH), Immunohistochemistry, Inflammatory myofibroblastic tumour (inflammatory pseudotumour), Molecular genetics, Neoplasia, Postoperative spindle cell nodule, Sarcoma, Soft tissue tumour, Spindle cell lesions, Urinary bladder",
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T1 - Inflammatory myofibroblastic tumour of the urinary bladder

T2 - The role of immunoglobulin G4 and the comparison of two immunohistochemical antibodies and fluorescence in-situ hybridization for the detection of anaplastic lymphoma kinase alterations

AU - Choi, Euna

AU - Williamson, Sean R.

AU - Montironi, Rodolfo

AU - Zhang, Shaobo

AU - Wang, Mingsheng

AU - Eble, John

AU - Grignon, David

AU - Lopez-Beltran, Antonio

AU - Idrees, Muhammad

AU - Baldridge, Lee Ann

AU - Scarpelli, Marina

AU - Jones, Carol L.

AU - Wang, Lisha

AU - Maclennan, Gregory T.

AU - Osunkoya, Adeboye O.

AU - Cheng, Liang

PY - 2015/7/1

Y1 - 2015/7/1

N2 - Aims: We examined gene rearrangement and the expression of anaplastic lymphoma kinase (ALK) in urinary bladder inflammatory myofibroblastic tumour (IMT) using fluorescence in-situ hybridization (FISH) and two immunohistochemical antibodies to ALK. We also investigated whether IMT represents an immunoglobulin (Ig)G4-related disease. Methods and results: The performance of the Dako FLEX ALK monoclonal antibody (CD246) and the Cell Signaling Technology ALK (D5F3) XP monoclonal antibody were compared. Overall, 11 of 16 tumours showed ALK expression by immunohistochemistry (69%). Ten demonstrated ALK expression with both stains and one was positive with D5F3 but not CD246 (91% correlation). The D5F3 antibody yielded a stronger staining intensity and a higher sensitivity. Nine tumours demonstrated ALK rearrangements (56%) by FISH. Three were ALK+ by immunohistochemistry but negative for rearrangement by FISH, whereas one showed rearrangement by FISH but was negative by immunohistochemistry. In total, 12 tumours were positive for ALK abnormalities (75%). Using current criteria, no cases were classified as an IgG4-related disease. Conclusions: The ALK D5F3 immunohistochemical stain showed superior staining characteristics compared with ALK CD246. Discrepancies in the results between FISH and immunohistochemistry for ALK abnormalities may have causes that are multifactorial. By current criteria, IMT does not represent an IgG4-related disease.

AB - Aims: We examined gene rearrangement and the expression of anaplastic lymphoma kinase (ALK) in urinary bladder inflammatory myofibroblastic tumour (IMT) using fluorescence in-situ hybridization (FISH) and two immunohistochemical antibodies to ALK. We also investigated whether IMT represents an immunoglobulin (Ig)G4-related disease. Methods and results: The performance of the Dako FLEX ALK monoclonal antibody (CD246) and the Cell Signaling Technology ALK (D5F3) XP monoclonal antibody were compared. Overall, 11 of 16 tumours showed ALK expression by immunohistochemistry (69%). Ten demonstrated ALK expression with both stains and one was positive with D5F3 but not CD246 (91% correlation). The D5F3 antibody yielded a stronger staining intensity and a higher sensitivity. Nine tumours demonstrated ALK rearrangements (56%) by FISH. Three were ALK+ by immunohistochemistry but negative for rearrangement by FISH, whereas one showed rearrangement by FISH but was negative by immunohistochemistry. In total, 12 tumours were positive for ALK abnormalities (75%). Using current criteria, no cases were classified as an IgG4-related disease. Conclusions: The ALK D5F3 immunohistochemical stain showed superior staining characteristics compared with ALK CD246. Discrepancies in the results between FISH and immunohistochemistry for ALK abnormalities may have causes that are multifactorial. By current criteria, IMT does not represent an IgG4-related disease.

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KW - Carcinosarcoma

KW - Fluorescence in-situ hybridization (FISH)

KW - Immunohistochemistry

KW - Inflammatory myofibroblastic tumour (inflammatory pseudotumour)

KW - Molecular genetics

KW - Neoplasia

KW - Postoperative spindle cell nodule

KW - Sarcoma

KW - Soft tissue tumour

KW - Spindle cell lesions

KW - Urinary bladder

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DO - 10.1111/his.12619

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