Detection of EGFR Mutation using Cerebrospinal Fluid in Lung Adenocarcinoma with Central Nervous System Metastases

檢測腦脊髓液中具有中樞神經系統轉移肺腺癌病患之EGFR突變

背景：雖然過去研究的結果指出，Cobas® EGFR Mutation Test v2 試劑套組可以於腦脊髓液中檢測表皮生長因子受體 (EGFR) 基因的突變; 然而，關於檢體的有效性和品質，卻未有相關評估的結果。因此，利用腦脊髓液進行 EGFR 突變的檢測，需要進一步的研究，以提高檢體的有效性，並改善檢體的處理。
材料與方法：針對22例肺腺癌腦或軟腦膜轉移患者，我們分析其腦脊髓液細胞學以及 EGFR 突變檢測的結果。
結果：使用腦脊髓液檢體離心後的上清液進行 EGFR 突變檢測時，相較於沒有軟腦膜轉移的患者，有軟腦膜轉移的患者其檢體的有效性和突變檢出率顯著較高（28.6% vs. 71.4%, 費雪氏精確性檢定 P=0.024）。腦轉移和細胞學檢測的結果則和腦脊髓液檢體有效性以及 EGFR 突變檢出率無關。針對11 名腦脊髓液上清液未檢出 EGFR 突變的患者，若利用其腦脊髓液檢體離心後的沈澱物進行檢測，則有4名患者的腦脊髓液沈澱物可以萃取出有效的去氧核醣核酸，同時，EGFR 突變可於其中3名患者檢出。
結論：我們的研究除了證明Cobas® EGFR Mutation Test v2 試劑套組可以於腦脊髓液檢體中偵測 EGFR 突變外，同時，研究結果也提供改善檢體選擇和檢體處理的參考。

Background: Previous studies have revealed that the Cobas® EGFR Mutation Test v2 kit can detect epidermal growth factor receptor (EGFR) mutation in cerebrospinal fluid (CSF); however, the sample validity and quality have not yet been evaluated. Therefore, clinical methods and improved sample processing are required to improve EGFR mutation analysis using CSF samples.
Materials and Methods: We obtained CSF cytological examination and EGFR mutation analysis results of 22 patients with brain or leptomeningeal metastases due to lung adenocarcinoma.
Results: Compared to patients without leptomeningeal metastasis, those with leptomeningeal metastasis had significantly increased sample validity and EGFR mutation detection rates when CSF supernatant was used for mutation analysis (28.6% vs. 71.4%, P = 0.024 by Fisher’s exact test). In contrast, neither brain metastases nor cytological results were substantially associated with the sample validity or the EGFR detection rate. In 11 patients with invalid CSF supernatant, 4 patients had valid extracted DNA samples from CSF pellets. Of these 4, 3 had detectable EGFR mutation alleles.
Conclusion: Our study demonstrates the capability of the Cobas® EGFR Mutation Test v2 kit for detecting EGFR mutations in CSF samples and provides insights into sample selection and processing required for this kit.