Rabbit Anti-Human beta Catenin monoclonal antibody, clone F358

Background: Many patients with advanced non-small cell lung cancer manifested with metastasis, and molecular heterogeneity may exhibit between primary and metastatic tumors. We sought to investigate the clinical detection strategy of primary and metastatic tumors in Chinese patients with NSCLC. Methods: Here, 77 paired tumors of Chinese patients with lung adenocarcinoma were analyzed, and 1836 mutation in hotspot regions of 22 genes were identified by next-generation sequencing. The expression of ALK in these paired tumors was also detected by immunohistochemistry. Results: The results showed that the concordance rate in multiple pulmonary nodules, primary-LN metastasis pairs and primary-distant metastasis pairs was 67.7%, 94.1% and 86.7%, respectively. In multiple pulmonary nodules, the concordance rate was 100% when the pathologic diagnosis was intrapulmonary metastasis, whereas the concordance rate was 23.1% when the pathologic diagnosis was multiple primary tumors. TP53 and CTNNB1 mutations were detected as the recurrent alterations in LN metastasis. Moreover, the concordance of ALK status was observed in these pairs. Conclusions: Our data suggested that hotspot mutations and ALK status in the primary-metastasis pairs had a high concordance in lung adenocarcinoma. Clinical detection of one lesion may be enough to identify the key alterations except that patients are diagnosed with multiple primary tumors or have disease progression after benefiting from target therapy.

Background Patients with brain metastases (BMs) have a poor prognosis and limited therapeutic options. Lung cancer is the most common primary malignancy giving rise to BMs; thus, understanding the molecular mechanisms behind increased BM risk is essential for identifying therapeutic targets and developing effective interventions. Methods Sixty-one patients who underwent surgical resection of primary non-small cell lung cancer (NSCLC) and BMs were retrospectively studied. Comprehensive genomic profiling of primary NSCLC and matched BMs was performed with next-generation sequencing targeting 416 cancer-relevant genes. Results Mutations of major drivers, including EGFR, KRAS, TP53, and ALK, were highly concordant between primary NSCLC and matched BMs (>80%), whereas discordance suggested the unique genomic evolution and oncogenic mechanisms of NSCLC BMs. BMs also demonstrated higher levels of copy number variations in comparison with primary NSCLC. Furthermore, the alterations of genes encoding CDK4/CCND1, CDKN2A/2B, and PI3K signaling pathways were enriched in BMs, and this suggested their correlation with increased metastatic risk. Indeed, patients with activated PI3K signaling in their primary NSCLC had significantly shorter BM-free survival (hazard ratio, 8.49; P = .0005). In addition, mutated TP53 or an activated WNT pathway via CTNNB1, APC, and AXIN2 mutations trended toward shorter BM-free intervals but not significantly so. Conclusions These findings yield detailed insights into the genomic complexity and heterogeneity of primary NSCLC and matched BMs. This study highlights the significant correlation of PI3K signaling with increased metastatic risk in patients with NSCLC and identifies genomic alterations enriched in NSCLC BMs that could serve as prognostic markers and potential therapeutic targets for treating patients with NSCLC BMs.