Abstract
BACKGROUND: Anaplastic lymphoma kinase (ALK) rearrangement represents a landmark in the targeted therapy of non–small cell lung cancer (NSCLC). Immunohistochemistry (IHC) is a sensitive and specific method to detect ALK protein expression, possibly an alternative to fluorescence in situ hybridization (FISH). In this study, the concordance of FISH and IHC to determine ALK status was evaluated, particularly focusing on discordant cases. MATERIALS AND METHODS: ALK status was tested by FISH and the IHC validated method (Ventana ALK (D5F3) CDx Assay) in 95 NSCLCs. Discordant cases were analyzed also by next-generation sequencing (NGS). The response to crizotinib of treated patients was recorded. RESULTS: Seven (7.3%) discordant cases were ALK FISH positive and IHC negative. They showed coexistent split signals pattern, with mean percentage of 15.4%, and 5′ deletions pattern, with mean percentage 31.7%. Two cases had also gene amplification pattern. In three cases (42.8 %), the polysomy was observed. The NGS assay confirmed IHC results. In these patients, the treatment with crizotinib was ineffective. CONCLUSIONS: In our discordant cases, a coexistent complex pattern (deleted, split, and amplified/polysomic) of ALK gene was observed by FISH analysis. These complex rearranged cases were not detectable by IHC, and it could be speculated that more complex biological mechanisms could modulate protein expression. These data highlight the role of IHC and underscore the complexity of the genetic pattern of ALK. It could be crucial to consider these findings in order to best select patients for anti-ALK treatment in daily clinical practice.
| Original language | English |
|---|---|
| Pages (from-to) | 389-395 |
| Number of pages | 7 |
| Journal | Translational Oncology |
| Volume | 12 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 1 2019 |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
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Discordance between FISH, IHC, and NGS Analysis of ALK Status in Advanced Non–Small Cell Lung Cancer (NSCLC) : a Brief Report of 7 Cases. / Scattone, Anna; Catino, Annamaria; Schirosi, Laura; Caldarola, Lucia; Tommasi, Stefania; Lacalamita, Rosanna; Montagna, Elisabetta Sara; Galetta, Domenico; Serio, Gabriella; Zito, Francesco Alfredo; Mangia, Anita.
In: Translational Oncology, Vol. 12, No. 2, 01.02.2019, p. 389-395.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Discordance between FISH, IHC, and NGS Analysis of ALK Status in Advanced Non–Small Cell Lung Cancer (NSCLC)
T2 - a Brief Report of 7 Cases
AU - Scattone, Anna
AU - Catino, Annamaria
AU - Schirosi, Laura
AU - Caldarola, Lucia
AU - Tommasi, Stefania
AU - Lacalamita, Rosanna
AU - Montagna, Elisabetta Sara
AU - Galetta, Domenico
AU - Serio, Gabriella
AU - Zito, Francesco Alfredo
AU - Mangia, Anita
PY - 2019/2/1
Y1 - 2019/2/1
N2 - BACKGROUND: Anaplastic lymphoma kinase (ALK) rearrangement represents a landmark in the targeted therapy of non–small cell lung cancer (NSCLC). Immunohistochemistry (IHC) is a sensitive and specific method to detect ALK protein expression, possibly an alternative to fluorescence in situ hybridization (FISH). In this study, the concordance of FISH and IHC to determine ALK status was evaluated, particularly focusing on discordant cases. MATERIALS AND METHODS: ALK status was tested by FISH and the IHC validated method (Ventana ALK (D5F3) CDx Assay) in 95 NSCLCs. Discordant cases were analyzed also by next-generation sequencing (NGS). The response to crizotinib of treated patients was recorded. RESULTS: Seven (7.3%) discordant cases were ALK FISH positive and IHC negative. They showed coexistent split signals pattern, with mean percentage of 15.4%, and 5′ deletions pattern, with mean percentage 31.7%. Two cases had also gene amplification pattern. In three cases (42.8 %), the polysomy was observed. The NGS assay confirmed IHC results. In these patients, the treatment with crizotinib was ineffective. CONCLUSIONS: In our discordant cases, a coexistent complex pattern (deleted, split, and amplified/polysomic) of ALK gene was observed by FISH analysis. These complex rearranged cases were not detectable by IHC, and it could be speculated that more complex biological mechanisms could modulate protein expression. These data highlight the role of IHC and underscore the complexity of the genetic pattern of ALK. It could be crucial to consider these findings in order to best select patients for anti-ALK treatment in daily clinical practice.
AB - BACKGROUND: Anaplastic lymphoma kinase (ALK) rearrangement represents a landmark in the targeted therapy of non–small cell lung cancer (NSCLC). Immunohistochemistry (IHC) is a sensitive and specific method to detect ALK protein expression, possibly an alternative to fluorescence in situ hybridization (FISH). In this study, the concordance of FISH and IHC to determine ALK status was evaluated, particularly focusing on discordant cases. MATERIALS AND METHODS: ALK status was tested by FISH and the IHC validated method (Ventana ALK (D5F3) CDx Assay) in 95 NSCLCs. Discordant cases were analyzed also by next-generation sequencing (NGS). The response to crizotinib of treated patients was recorded. RESULTS: Seven (7.3%) discordant cases were ALK FISH positive and IHC negative. They showed coexistent split signals pattern, with mean percentage of 15.4%, and 5′ deletions pattern, with mean percentage 31.7%. Two cases had also gene amplification pattern. In three cases (42.8 %), the polysomy was observed. The NGS assay confirmed IHC results. In these patients, the treatment with crizotinib was ineffective. CONCLUSIONS: In our discordant cases, a coexistent complex pattern (deleted, split, and amplified/polysomic) of ALK gene was observed by FISH analysis. These complex rearranged cases were not detectable by IHC, and it could be speculated that more complex biological mechanisms could modulate protein expression. These data highlight the role of IHC and underscore the complexity of the genetic pattern of ALK. It could be crucial to consider these findings in order to best select patients for anti-ALK treatment in daily clinical practice.
UR - http://www.scopus.com/inward/record.url?scp=85057882337&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85057882337&partnerID=8YFLogxK
U2 - 10.1016/j.tranon.2018.11.006
DO - 10.1016/j.tranon.2018.11.006
M3 - Article
AN - SCOPUS:85057882337
VL - 12
SP - 389
EP - 395
JO - Translational Oncology
JF - Translational Oncology
SN - 1936-5233
IS - 2
ER -