Clinicopathologic characteristics of ALK rearrangements in primary lung adenocarcinoma with identified EGFR and KRAS status.
OBJECTIVE
EGFR and KRAS genes and ALK arrangements are three genetic drivers of lung adenocarcinoma. The aim of this study was to investigate the clinicopathologic characteristics of the ALK rearrangements in patients with primary lung adenocarcinoma and with identified EGFR or KRAS status.


METHODS
Patients with primary lung adenocarcinoma who had enough tissue for study were enrolled. EGFR and KRAS status were identified by DNA sequencing. ALK rearrangements were detected in a tissue microarray by using fluorescent in situ hybridization.


RESULTS
Of 332 patients with primary lung adenocarcinoma, the frequency of the EGFR or the KRAS mutations, and the ALK rearrangements were 44.9% (149/332), 7.2% (24/332), and 9.6% (32/332), respectively. Only one (1/332, 0.3%) patient had the coexistence of the EGFR mutation (L858R at exon 21) and the ALK rearrangement. Compared with ALK-negative patients, ALK-positive patients were significantly younger (P < 0.001). The incidence of the ALK rearrangements was much higher in EGFR wild-type patients than in those with EGFR mutations (P < 0.001). There was no difference in the gender, smoking, disease stage, or histologic subtypes between the ALK-positive patients and the ALK-negative patients.


CONCLUSIONS
The ALK rearrangements are independently associated with younger age and the EGFR wild type. The EGFR mutations and the ALK rearrangements are rarely coexistent. The ALK rearrangements and the KRAS mutations are mutually exclusive.
Department of Medical Oncology, Beijing Thoracic Tumor and Tuberculosis Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, China.
Jinghui
J
Wang
Yujie
Y
Dong
Yiran
Y
Cai
Lijuan
L
Zhou
Shafei
S
Wu
Guimei
G
Liu
Dan
D
Su
Xi
X
Li
Na
N
Qin
Jingying
J
Nong
Hongyan
H
Jia
Quan
Q
Zhang
Jing
J
Mu
Xuan
X
Zeng
Haiqing
H
Zhang
Shucai
S
Zhang
Zongde
Z
Zhang
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D046888:Tissue Array Analysis; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins