TY - JOUR
T1 - The prevalence of ALK rearrangement in pulmonary adenocarcinomas in an unselected Caucasian population from a defined catchment area
T2 - impact of smoking
AU - Skov, Birgit G
AU - Clementsen, Paul
AU - Larsen, Klaus R
AU - Sørensen, Jens B
AU - Mellemgaard, Anders
N1 - © 2016 John Wiley & Sons Ltd.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - AIMS: To assess the prevalence of EML4-ALK rearrangement gene measured by immunohistochemistry in an unselected population-based consecutive cohort of patients with adenocarcinoma of the lung (ACL), and the correlation with smoking history, thyroid transcription factor 1 (TTF1), gender and age.METHODS AND RESULTS: All patients diagnosed in the population of the greater Copenhagen area were included, irrespective of gender, age, smoking habits, stage or type of available diagnostic material. Tumours were stained with immunohistochemistry (clone 5A4). Immunohistochemistry-positive tumours were tested by fluorescence in-situ hybridization (FISH). During a 16-month period, 760 patients in the population were diagnosed with ACL. In 2.6% there was insufficient material for ALK testing (20 of 760). Eleven per cent of the remaining 740 ACL patients were never smokers, 43% were ex-smokers smokers and 46% were current smokers. Fourteen patients [1.9%, 95% confidence interval (CI) = 1.1-3.2] were ALK-positive by immunohistochemistry. Nine of 82 never-smokers (11%, 95% CI = 5.9-19.6) and five of 652 ex- or current smokers (0.8%, 95% CI = 0.4-2.1) were ALK-positive. Only two ALK-positive patients were found among 586 heavy smokers (> 15 pack-years) (0.3%, 95% CI = 0.09-1.2). Thirteen of the 14 immunohistochemistry-positive patients were FISH-positive. All ALK-positive tumours were TTF1-positive. The number needed to test (NNT) to identify one ALK positive patient was 9, 22 and 293 among never smokers, light and heavy smokers, respectively.CONCLUSIONS: Immunohistochemical analysis of ALK rearrangement was possible in 97.4% of patients. ALK rearrangement was found primarily in never smokers. NNT to identify one ALK-positive patient was 9, 22 and 293 among never smokers, light and heavy smokers, respectively.
AB - AIMS: To assess the prevalence of EML4-ALK rearrangement gene measured by immunohistochemistry in an unselected population-based consecutive cohort of patients with adenocarcinoma of the lung (ACL), and the correlation with smoking history, thyroid transcription factor 1 (TTF1), gender and age.METHODS AND RESULTS: All patients diagnosed in the population of the greater Copenhagen area were included, irrespective of gender, age, smoking habits, stage or type of available diagnostic material. Tumours were stained with immunohistochemistry (clone 5A4). Immunohistochemistry-positive tumours were tested by fluorescence in-situ hybridization (FISH). During a 16-month period, 760 patients in the population were diagnosed with ACL. In 2.6% there was insufficient material for ALK testing (20 of 760). Eleven per cent of the remaining 740 ACL patients were never smokers, 43% were ex-smokers smokers and 46% were current smokers. Fourteen patients [1.9%, 95% confidence interval (CI) = 1.1-3.2] were ALK-positive by immunohistochemistry. Nine of 82 never-smokers (11%, 95% CI = 5.9-19.6) and five of 652 ex- or current smokers (0.8%, 95% CI = 0.4-2.1) were ALK-positive. Only two ALK-positive patients were found among 586 heavy smokers (> 15 pack-years) (0.3%, 95% CI = 0.09-1.2). Thirteen of the 14 immunohistochemistry-positive patients were FISH-positive. All ALK-positive tumours were TTF1-positive. The number needed to test (NNT) to identify one ALK positive patient was 9, 22 and 293 among never smokers, light and heavy smokers, respectively.CONCLUSIONS: Immunohistochemical analysis of ALK rearrangement was possible in 97.4% of patients. ALK rearrangement was found primarily in never smokers. NNT to identify one ALK-positive patient was 9, 22 and 293 among never smokers, light and heavy smokers, respectively.
KW - Adenocarcinoma/genetics
KW - Adult
KW - Aged
KW - DNA-Binding Proteins/biosynthesis
KW - European Continental Ancestry Group
KW - Female
KW - Gene Rearrangement
KW - Humans
KW - Immunohistochemistry
KW - In Situ Hybridization, Fluorescence
KW - Lung Neoplasms/genetics
KW - Male
KW - Middle Aged
KW - Oncogene Proteins, Fusion/genetics
KW - Smoking/adverse effects
KW - Transcription Factors
U2 - 10.1111/his.13148
DO - 10.1111/his.13148
M3 - Journal article
C2 - 27943404
SN - 0309-0167
VL - 70
SP - 889
EP - 895
JO - Histopathology
JF - Histopathology
IS - 6
ER -