High concordance of ALK rearrangement between primary tumor and paired metastatic lymph node in patients with lung adenocarcinoma.
BACKGROUND
Lung cancer has heterogeneous features. It remains unclear whether ALK rearrangement was distributed heterogeneously in tumor from different anatomic sites. To address this issue, we investigate the concordance of ALK rearrangement between primary tumors and paired metastatic lymph nodes in pulmonary adenocarcinoma patients.


METHODS
From Sep 2013 to May 2014, resectable lung adenocarcinoma patients with EGFR wildtype and paired metastatic lymph nodes from Tongji University affiliated Shanghai pulmonary hospital were selected into this study. An auto-mated Ventana ALK with clone D5F3 antibody immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to detected ALK rearrangement. Discordant cases between IHC and RT-PCR were further validated by fluorescence in situ hybridization (FISH).


RESULTS
A total of 101 patients were enrolled into this study with a median age of 60 years old (range, 35-78 years). ALK rearrangement was found in 20 primary lesions, while in 18 paired metastatic lymph nodes. ALK rearrangement was more frequently happened in younger (P<0.001), Nonsmokers (P=0.012), high-stage disease (P=0.021) and predominantly solid growth pattern (P=0.024). The concordance rate between primary tumor and paired metastatic lymph nodes was 98%. Two patients with ALK rearrangement on primary tumor didn't show ALK gene fusion on paired metastatic lymph nodes. Sixty-eight cases had more than two stations of metastatic lymph nodes. ALK rearrangement in the different station of metastatic lymph nodes of the same patient was consistent.


CONCLUSIONS
High concordant rate of ALK rearrangement between primary tumors and paired metastatic lymph nodes were found in this study. The authors concluded that specimens from metastatic lesions and primary tumors are equally suitable for detection ALK rearrangement.
1 Department of Pathology, 2 Department of Medical Oncology, 3 Central Lab, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China ; 4 Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Likun
L
Hou
1 Department of Pathology, 2 Department of Medical Oncology, 3 Central Lab, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China ; 4 Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Shengxiang
S
Ren
1 Department of Pathology, 2 Department of Medical Oncology, 3 Central Lab, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China ; 4 Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Bo
B
Su
1 Department of Pathology, 2 Department of Medical Oncology, 3 Central Lab, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China ; 4 Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Liping
L
Zhang
1 Department of Pathology, 2 Department of Medical Oncology, 3 Central Lab, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China ; 4 Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Wei
W
Wu
1 Department of Pathology, 2 Department of Medical Oncology, 3 Central Lab, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China ; 4 Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Wei
W
Zhang
1 Department of Pathology, 2 Department of Medical Oncology, 3 Central Lab, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China ; 4 Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Zhengwei
Z
Dong
1 Department of Pathology, 2 Department of Medical Oncology, 3 Central Lab, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China ; 4 Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Yan
Y
Huang
1 Department of Pathology, 2 Department of Medical Oncology, 3 Central Lab, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China ; 4 Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Chunyan
C
Wu
1 Department of Pathology, 2 Department of Medical Oncology, 3 Central Lab, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China ; 4 Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Gang
G
Chen
ALK rearrangement; fluorescence in situ hybridization (FISH); heterogeneity; immunohistochemistry (IHC); lung adenocarcinoma; reverse transcriptase-polymerase chain reaction (RT-PCR)