Article
MET mutation status does not predict outcome in patients with non-small cell lung cancer brain metastases
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Authors
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Silvia Hernández-Durán
- Universitätsmedizin Göttingen, Klinik für Neurochirurgie, Göttingen, Deutschland
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Christina Wolfert
- Universitätsmedizin Göttingen, Klinik für Neurochirurgie, Göttingen, Deutschland
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Alonso Barrantes Freer
- Universitätsmedizin Göttingen, Institut für Neuropathologie, Göttingen, Deutschland
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Abdelhalim Hussein
- Universitätsmedizin Göttingen, Klinik für Neurochirurgie, Göttingen, Deutschland
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Veit Rohde
- Universitätsmedizin Göttingen, Klinik für Neurochirurgie, Göttingen, Deutschland
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Annalen Bleckmann
- Universitätsmedizin Göttingen, Klinik für Hämato-Onkologie, Göttingen, Deutschland
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Bawarjan Schatlo
- Universitätsmedizin Göttingen, Klinik für Neurochirurgie, Göttingen, Deutschland
| Published: | June 18, 2018 |
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Outline
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Objective: MET signaling has been proven to be critical for aggressive behavior in non-small cell lung cancer (NSCLC), and it is often regarded as a late event in NSCLC natural history. MET expression and phosphorylation have also been associated with the development of NSCLC brain metastasis and have selectively been enriched in brain metastases relative to paired primary lung tumors. No studies have assessed the predictive value of MET amplification in regards to outcome of patients with NSCLC brain metastases. In this study, we aim to investigate whether or not MET amplification correlates with negative outcome in patients with NSCLC brain metastases.
Methods: We analyzed patients enrolled into the prospective Metastasys trial harboring brain metastases from NSCLC who underwent MET mutation analysis in brain specimens. Analysis was performed with real-time PCR assays for MET amplification status. Overall survival was calculated, and survival curves of patients harboring MET amplifications were compared to those of patients labeled as MET negative.Statistical analysis was performed with IBM® SPSS® V. 21.
Results: A total of 31 patients harboring NSCLC brain metastases were included. MET mutation was observed in n=11, 35% of cases. Low level, intermediate level, and high level MET amplification were observed in n=7/11, 63.6%; n=4/11, 36.4%; and n=3/11, 27.3%, respectively. MET negative and MET mutant groups were matched for age and adjuvant therapy (one-way ANOVA revealed no statistically significant difference). Median overall survival was 18.1 months (range: 0.5-80.9 months). Subjects without MET amplification had median overall survival of 11.5 months (range: 8.3-15.2 months). Subjects with low level MET amplification had median overall survival of 15 months (range: 11.6-47.5 months). Subjects with intermediate level MET amplification had median overall survival of 63.1 months (range: 54.6-89.4 months). Subjects with high level MET amplification had median overall survival of 30.2 months (range: 28.5-35.4 months). A log rank test did not reveal a statistically significant difference among groups, χ2(2)=4.299, p=.231.
Conclusion: Our results do not support the notion that MET mutation has a major impact on survival in patients harboring NSCLC brain metastases undergoing surgical resection. While MET might be implicated in the development of NSCLC brain metastases in some patients, its presence does not appear to predict a worse outcome once patients have developed cerebral involvement.
