Homogeneity and High Concordance of ALK Translocation in Primary Lung Adenocarcinoma and Paired Lymph Node Metastasis

Abstract

Translocation of anaplastic lymphoma kinase (ALK) gene is an important determinator for the response to ALK tyrosine kinase inhibitor (TKI) in non-small-cell lung cancer (NSCLC) patients. The existence of genetic heterogeneity will affect the results of molecular testing, especially in biopsy samples from primary or metastatic sites of patients with advanced stage NSCLC. We intended to explore the heterogeneity of ALK gene translocation in excision specimens and to examine the existence of discordance of ALK status between primary tumours and corresponding lymph node metastases. A total of 106 ALK positive lung adenocarcinoma cases were collected for assessment of intratumour heterogeneity of ALK gene translocation, which were stained by the fully automated Ventana ALK D5F3 immunohistochemistry (IHC) analysis. In addition, the ALK gene translocations were evaluated in a series of 53 primary tumours and their paired lymph node metastases using ALK D5F3 IHC staining. The concordance rate between primary tumours and paired metastatic lymph nodes was 100%. ALK status was homogeneous in lung adenocarcinoma samples and was generally stable during metastasis. Therefore, ALK gene translocation can be measured reliably in material from either primary or metastatic tumours in lung adenocarcinoma patients.