High concordance of ALK rearrangement between primary tumor and paired metastatic lymph node in patients with lung adenocarcinoma

Abstract

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. 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.

A comparison of ALK gene rearrangement and ALK protein expression in primary lung carcinoma and matched metastasis

“…However, the possibility of a low protein expression of the rearranged transcript, the fact that ALK rearrangement leads to a non‐translated transcript or, as mentioned above, the fact that we used archival tissue, may also be considered as an alternative explanation for the ALK IHC false‐negative cases. Similar to the study by Hou et al ., in our study ALK IHC showed a high concordance of 94% between primary tumour and matched metastases . This result is in agreement with other reports suggesting strongly that ALK IHC can be used as a screening test …”

“…However, recent studies using the next‐generation sequencing (NGS) approach mainly over‐ruled the concept of oncogenic somatic mutations heterogeneity, and attributed the previous observations to different testing methods and sampling issues . Conversely, similar studies looking into gene rearrangements are uncommon . As the majority of lung adenocarcinomas are diagnosed at an advanced stage with evidence of metastasis, the question remains as to whether the primary or the metastatic tumour should be submitted for molecular studies.…”

“…24,25 Conversely, similar studies looking into gene rearrangements are uncommon. [26][27][28][29][30][31] As the majority of lung adenocarcinomas are diagnosed at an advanced stage with evidence of metastasis, the question remains as to whether the primary or the metastatic tumour should be submitted for molecular studies. The aim of this study was to compare ALK gene rearrangement and ALK protein expression status between primary lung adenocarcinomas and matched metastasis.…”

Clonally‐related primary ALK rearranged adenocarcinoma and associated metastatic lesions

“…Hou et al . explored the status of ALK rearrangements between primary tumors and paired metastatic lymph nodes in 101 patients with lung adenocarcinomas . The concordance rate of ALK rearrangements between primary tumors and paired metastatic lymph nodes was 98%.…”

“…evaluated the ALK gene in 78 paired specimens (primary tumor site and paired metastatic lymph nodes); 98.7% of the patients had concordant ALK rearrangements . However, these studies did not further analyze the histological classification between primary and metastatic lymph nodes . Few reports have simultaneously explored the intra‐tumor heterogeneity in histomorphology and molecular subtype between primary and paired metastatic tumors.…”