TY - JOUR
T1 - Inconsistent intersample alk fish results in patients with lung cancer
T2 - Analysis of potential causes
AU - Tang, Zhenya
AU - Chen, Hui
AU - Hong, Lingzhi
AU - Tang, Guilin
AU - Toruner, Gokce A.
AU - Wang, Wei
AU - Chowdhuri, Sinchita Roy
AU - Yin, Wei
AU - Jung, Hai Suk
AU - Gu, Jun
AU - Routbort, Mark J.
AU - Zhang, Jianjun
AU - Khoury, Joseph D.
AU - Medeiros, L. Jeffrey
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/7
Y1 - 2020/7
N2 - ALK FISH analyses of multiple specimens occasionally yield inconsistent intersample results in lung cancer patients, posing clinical challenges requiring intensive analysis of all potential causative pre-and post-analytic factors. In this study, 19 patients (8M/11F) with inconsistent intersample ALK FISH results were analyzed, representing 4.9% of patients assessed ≥ twice in our institution. Fifteen patients received ALK tyrosine kinase inhibitor(s) (TKIs). Nine patients died, and ten were alive for 8 to 74-month follow-ups (median, 40 months). Through strict and stringent laboratory and case-review policies, all postanalytic factors were excluded. Correlating clinical information, ALK results obtained by RNA sequencing (RNA-seq) and other concurrent tests, several pre-analytic factors were determined. A suboptimal specimen was likely the cause in three patients, supported by the failure of one or more concurrent tests or discrepant results between FISH and RNA-seq. ALK inhibition by TKIs might have been responsible for the change of ALK status from positive to negative in eight patients. Other potential explanations include the existence of multiple primary lung cancer lesions, tumor heterogeneity, and the clonal evolution of tumor cells, related or not to ALK TKI therapy. This study is helpful for both pathologists and clinicians encountering inconsistent and/or discrepant intersample results.
AB - ALK FISH analyses of multiple specimens occasionally yield inconsistent intersample results in lung cancer patients, posing clinical challenges requiring intensive analysis of all potential causative pre-and post-analytic factors. In this study, 19 patients (8M/11F) with inconsistent intersample ALK FISH results were analyzed, representing 4.9% of patients assessed ≥ twice in our institution. Fifteen patients received ALK tyrosine kinase inhibitor(s) (TKIs). Nine patients died, and ten were alive for 8 to 74-month follow-ups (median, 40 months). Through strict and stringent laboratory and case-review policies, all postanalytic factors were excluded. Correlating clinical information, ALK results obtained by RNA sequencing (RNA-seq) and other concurrent tests, several pre-analytic factors were determined. A suboptimal specimen was likely the cause in three patients, supported by the failure of one or more concurrent tests or discrepant results between FISH and RNA-seq. ALK inhibition by TKIs might have been responsible for the change of ALK status from positive to negative in eight patients. Other potential explanations include the existence of multiple primary lung cancer lesions, tumor heterogeneity, and the clonal evolution of tumor cells, related or not to ALK TKI therapy. This study is helpful for both pathologists and clinicians encountering inconsistent and/or discrepant intersample results.
KW - ALK
KW - Fluorescence in situ hybridization (FISH)
KW - Lung cancer
KW - Next-generation sequencing (NGS)
KW - RNA sequencing (RNA-seq)
KW - Tyrosine kinase inhibitor (TKI)
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U2 - 10.3390/cancers12071903
DO - 10.3390/cancers12071903
M3 - Article
C2 - 32674491
AN - SCOPUS:85087858933
SN - 2072-6694
VL - 12
SP - 1
EP - 17
JO - Cancers
JF - Cancers
IS - 7
M1 - 1903
ER -