gms | German Medical Science

Objective: Brain metastases (BM) constitute the most common type of central nervous system malignancies, and nearly half of them stem from lung cancers. Driver mutations have been identified in primary lung cancer, which have significantly enhanced the therapeutic options for patients harboring these genetic changes. EGFR mutations have been described in up to 10% of lung adenocarcinomas (ADC), while ALK/EML4 translocation, MET amplification and ROS1 fusion have been identified in up to 7%, 2% and 2%, respectively. To date, no comprehensive analysis of the molecular pathological profile of ADC BM has been performed.

Methods: We conducted a retrospective analysis of the molecular pathological profile of patients harboring BM from ADC who underwent tumor resection at our neurosurgical department from July 2013 to July 2016. EGFR mutations were determined in exons 18, 19, and 21; MET amplification was determined by FISH assays, as well as ALK/EML4 translocation, and ROS1 fusion.

Results: Our cohort included 57 (33 males, 24 females) patients harboring BM from ADC who underwent surgical resection. Of these, 48/57 (84%) underwent EGFR status analysis and three (3/48, 6%) exhibited mutations (two in exon 19, and one in exon 21). MET status was available in 26/57 (46%), of which 11 (42%) exhibited mutations; six were low level, four intermediate level, and one high level gains. ROS1 status was available in 45/57 (79%) patients, with only one mutation. ALK/EML4 translocation was determined in 48/57 (84%) patients, all of them negative.

Conclusion: Our retrospective analysis shows that the distribution of the mutations in ADC BM differs from their primary counterparts. Of note is the increased presence of MET mutations, which may lead to new therapeutic options in patients with ADC BM. Future studies need to address at which point in the natural history of ADC these mutation changes occur.