Accurate identification of ALK positive lung carcinoma patients: Novel FDA-cleared automated fluorescence in situ hybridization scanning system and ultrasensitive immunohistochemistry

Esther Conde, Ana Suárez-Gauthier, Amparo Benito, Pilar Garrido, Rosario García-Campelo, Michele Biscuola, Luis Paz-Ares, David Hardisson, Javier De Castro, M. Carmen Camacho, Delvys Rodriguez-Abreu, Ihab Abdulkader, Josep Ramirez, Noemí Reguart, Marta Salido, Lara Pijuán, Edurne Arriola, Julián Sanz, Victoria Folgueras, Noemí VillanuevaJavier Gómez-Román, Manuel Hidalgo, Fernando López-Ríos

Research output: Contribution to journalArticle

Abstract

Methods: Forty-seven ALK FISH-positive and 56 ALK FISH-negative NSCLC samples were studied. All specimens were screened for ALK expression by two IHC antibodies (clone 5A4 from Novocastra and clone D5F3 from Ventana) and for ALK rearrangement by FISH (Vysis ALK FISH break-apart kit), which was automatically captured and scored by using Bioview's automated scanning system.

Background: Based on the excellent results of the clinical trials with ALK-inhibitors, the importance of accurately identifying ALK positive lung cancer has never been greater. However, there are increasing number of recent publications addressing discordances between FISH and IHC. The controversy is further fuelled by the different regulatory approvals. This situation prompted us to investigate two ALK IHC antibodies (using a novel ultrasensitive detection-amplification kit) and an automated ALK FISH scanning system (FDA-cleared) in a series of non-small cell lung cancer tumor samples.

Results: All positive cases with the IHC antibodies were FISH-positive. There was only one IHC-negative case with both antibodies which showed a FISH-positive result. The overall sensitivity and specificity of the IHC in comparison with FISH were 98% and 100%, respectively.

Conclusions: The specificity of these ultrasensitive IHC assays may obviate the need for FISH confirmation in positive IHC cases. However, the likelihood of false negative IHC results strengthens the case for FISH testing, at least in some situations.

Original languageEnglish (US)
Article numbere107200
JournalPLoS One
Volume9
Issue number9
DOIs
StatePublished - Sep 23 2014
Externally publishedYes

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fluorescence in situ hybridization
Fluorescence In Situ Hybridization
carcinoma
immunohistochemistry
Fluorescence
Immunohistochemistry
lungs
Scanning
Carcinoma
Lung
antibodies
Antibodies
lung neoplasms
Clone Cells
clones
Non-Small Cell Lung Carcinoma
Amplification
Tumors
clinical trials
Assays

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Accurate identification of ALK positive lung carcinoma patients : Novel FDA-cleared automated fluorescence in situ hybridization scanning system and ultrasensitive immunohistochemistry. / Conde, Esther; Suárez-Gauthier, Ana; Benito, Amparo; Garrido, Pilar; García-Campelo, Rosario; Biscuola, Michele; Paz-Ares, Luis; Hardisson, David; De Castro, Javier; Camacho, M. Carmen; Rodriguez-Abreu, Delvys; Abdulkader, Ihab; Ramirez, Josep; Reguart, Noemí; Salido, Marta; Pijuán, Lara; Arriola, Edurne; Sanz, Julián; Folgueras, Victoria; Villanueva, Noemí; Gómez-Román, Javier; Hidalgo, Manuel; López-Ríos, Fernando.

In: PLoS One, Vol. 9, No. 9, e107200, 23.09.2014.

Research output: Contribution to journalArticle

Conde, E, Suárez-Gauthier, A, Benito, A, Garrido, P, García-Campelo, R, Biscuola, M, Paz-Ares, L, Hardisson, D, De Castro, J, Camacho, MC, Rodriguez-Abreu, D, Abdulkader, I, Ramirez, J, Reguart, N, Salido, M, Pijuán, L, Arriola, E, Sanz, J, Folgueras, V, Villanueva, N, Gómez-Román, J, Hidalgo, M & López-Ríos, F 2014, 'Accurate identification of ALK positive lung carcinoma patients: Novel FDA-cleared automated fluorescence in situ hybridization scanning system and ultrasensitive immunohistochemistry', PLoS One, vol. 9, no. 9, e107200. https://doi.org/10.1371/journal.pone.0107200
Conde, Esther ; Suárez-Gauthier, Ana ; Benito, Amparo ; Garrido, Pilar ; García-Campelo, Rosario ; Biscuola, Michele ; Paz-Ares, Luis ; Hardisson, David ; De Castro, Javier ; Camacho, M. Carmen ; Rodriguez-Abreu, Delvys ; Abdulkader, Ihab ; Ramirez, Josep ; Reguart, Noemí ; Salido, Marta ; Pijuán, Lara ; Arriola, Edurne ; Sanz, Julián ; Folgueras, Victoria ; Villanueva, Noemí ; Gómez-Román, Javier ; Hidalgo, Manuel ; López-Ríos, Fernando. / Accurate identification of ALK positive lung carcinoma patients : Novel FDA-cleared automated fluorescence in situ hybridization scanning system and ultrasensitive immunohistochemistry. In: PLoS One. 2014 ; Vol. 9, No. 9.
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abstract = "Methods: Forty-seven ALK FISH-positive and 56 ALK FISH-negative NSCLC samples were studied. All specimens were screened for ALK expression by two IHC antibodies (clone 5A4 from Novocastra and clone D5F3 from Ventana) and for ALK rearrangement by FISH (Vysis ALK FISH break-apart kit), which was automatically captured and scored by using Bioview's automated scanning system.Background: Based on the excellent results of the clinical trials with ALK-inhibitors, the importance of accurately identifying ALK positive lung cancer has never been greater. However, there are increasing number of recent publications addressing discordances between FISH and IHC. The controversy is further fuelled by the different regulatory approvals. This situation prompted us to investigate two ALK IHC antibodies (using a novel ultrasensitive detection-amplification kit) and an automated ALK FISH scanning system (FDA-cleared) in a series of non-small cell lung cancer tumor samples.Results: All positive cases with the IHC antibodies were FISH-positive. There was only one IHC-negative case with both antibodies which showed a FISH-positive result. The overall sensitivity and specificity of the IHC in comparison with FISH were 98{\%} and 100{\%}, respectively.Conclusions: The specificity of these ultrasensitive IHC assays may obviate the need for FISH confirmation in positive IHC cases. However, the likelihood of false negative IHC results strengthens the case for FISH testing, at least in some situations.",
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T1 - Accurate identification of ALK positive lung carcinoma patients

T2 - Novel FDA-cleared automated fluorescence in situ hybridization scanning system and ultrasensitive immunohistochemistry

AU - Conde, Esther

AU - Suárez-Gauthier, Ana

AU - Benito, Amparo

AU - Garrido, Pilar

AU - García-Campelo, Rosario

AU - Biscuola, Michele

AU - Paz-Ares, Luis

AU - Hardisson, David

AU - De Castro, Javier

AU - Camacho, M. Carmen

AU - Rodriguez-Abreu, Delvys

AU - Abdulkader, Ihab

AU - Ramirez, Josep

AU - Reguart, Noemí

AU - Salido, Marta

AU - Pijuán, Lara

AU - Arriola, Edurne

AU - Sanz, Julián

AU - Folgueras, Victoria

AU - Villanueva, Noemí

AU - Gómez-Román, Javier

AU - Hidalgo, Manuel

AU - López-Ríos, Fernando

PY - 2014/9/23

Y1 - 2014/9/23

N2 - Methods: Forty-seven ALK FISH-positive and 56 ALK FISH-negative NSCLC samples were studied. All specimens were screened for ALK expression by two IHC antibodies (clone 5A4 from Novocastra and clone D5F3 from Ventana) and for ALK rearrangement by FISH (Vysis ALK FISH break-apart kit), which was automatically captured and scored by using Bioview's automated scanning system.Background: Based on the excellent results of the clinical trials with ALK-inhibitors, the importance of accurately identifying ALK positive lung cancer has never been greater. However, there are increasing number of recent publications addressing discordances between FISH and IHC. The controversy is further fuelled by the different regulatory approvals. This situation prompted us to investigate two ALK IHC antibodies (using a novel ultrasensitive detection-amplification kit) and an automated ALK FISH scanning system (FDA-cleared) in a series of non-small cell lung cancer tumor samples.Results: All positive cases with the IHC antibodies were FISH-positive. There was only one IHC-negative case with both antibodies which showed a FISH-positive result. The overall sensitivity and specificity of the IHC in comparison with FISH were 98% and 100%, respectively.Conclusions: The specificity of these ultrasensitive IHC assays may obviate the need for FISH confirmation in positive IHC cases. However, the likelihood of false negative IHC results strengthens the case for FISH testing, at least in some situations.

AB - Methods: Forty-seven ALK FISH-positive and 56 ALK FISH-negative NSCLC samples were studied. All specimens were screened for ALK expression by two IHC antibodies (clone 5A4 from Novocastra and clone D5F3 from Ventana) and for ALK rearrangement by FISH (Vysis ALK FISH break-apart kit), which was automatically captured and scored by using Bioview's automated scanning system.Background: Based on the excellent results of the clinical trials with ALK-inhibitors, the importance of accurately identifying ALK positive lung cancer has never been greater. However, there are increasing number of recent publications addressing discordances between FISH and IHC. The controversy is further fuelled by the different regulatory approvals. This situation prompted us to investigate two ALK IHC antibodies (using a novel ultrasensitive detection-amplification kit) and an automated ALK FISH scanning system (FDA-cleared) in a series of non-small cell lung cancer tumor samples.Results: All positive cases with the IHC antibodies were FISH-positive. There was only one IHC-negative case with both antibodies which showed a FISH-positive result. The overall sensitivity and specificity of the IHC in comparison with FISH were 98% and 100%, respectively.Conclusions: The specificity of these ultrasensitive IHC assays may obviate the need for FISH confirmation in positive IHC cases. However, the likelihood of false negative IHC results strengthens the case for FISH testing, at least in some situations.

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