Vinayanuwattikun Chanida, Mingmalairak Siyamol, Jittapiromsak Nutchawan, Thaipisuttikul Iyavut, Sriuranpong Virote, Mutirangura Apiwat, Shuangshoti Shanop
Department of Medicine, Faculty of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital, Bangkok, 10330, Thailand.
Department of Radiology, Faculty of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital, Bangkok, 10330, Thailand.
J Neurooncol. 2016 Sep;129(3):395-403. doi: 10.1007/s11060-016-2199-5. Epub 2016 Jul 11.
Current diagnostic methods for leptomeningeal metastasis (LM) from epithelial-derived malignancy (EDM) have limited sensitivity. Here, we explored SHP-1 promoter 2 methylation (SHP1P2)-an epithelial-specific methylation marker previously proven as risk stratification and potential diagnostic marker in non-small cell lung cancer-for EDM with LM. We prospectively recruited 136 patients who were diagnosed EDM with LM (n = 25), EDM without LM (n = 14), non-EDM with LM (n = 8), and benign meningeal diseases (n = 89). The primary cancer sites for EDM with LM were lung (n = 17), breast (n = 5), and colon (n = 3). We performed quantitative analyses of cell-free (cfSHP1P2) and whole fraction (wSHP1P2) from cerebrospinal fluid (CSF); results were correlated with the clinicopathological data, including CSF cytology. Median cfSHP1P2 and wSHP1P2 were 3.08 [range: 0-163.5] and 9.35 [0.69-91.63] ng/ml, respectively, in EDM with LM; 0 [0-0.08] and 0.23 [0-7.84] ng/ml in EDM without LM; and were undetectable in most cases of benign meningeal diseases and non-EDM with LM. The cut-off values of 0.22 ng/ml for methylated cfSHP1P2 and 0.59 ng/ml for wSHP1P2 were the best to discriminate EDM with LM from EDM without LM (sensitivity: 79-100 %; specificity: 83-100 %), as well as from other benign conditions (sensitivity: 85-100 % specificity: 78-100 %). CSF cytology yielded 76 % sensitivity for diagnosing EDM with LM. Further validation of CSF SHP1P2 methylation detection as a role of adjunctive tool for LM from EDM should be interested based on our study.
目前用于诊断上皮源性恶性肿瘤（EDM）软脑膜转移（LM）的方法敏感性有限。在此，我们探索了SHP-1启动子2甲基化（SHP1P2）——一种上皮特异性甲基化标志物，先前已被证明可作为非小细胞肺癌的风险分层和潜在诊断标志物——用于诊断伴有LM的EDM。我们前瞻性招募了136例患者，其中诊断为伴有LM的EDM（n = 25）、不伴有LM的EDM（n = 14）、伴有LM的非EDM（n = 8）以及良性脑膜疾病（n = 89）。伴有LM的EDM的原发癌部位为肺（n = 17）、乳腺（n = 5）和结肠（n = 3）。我们对脑脊液（CSF）中的游离（cfSHP1P2）和全部分数（wSHP1P2）进行了定量分析；结果与临床病理数据相关，包括CSF细胞学检查。伴有LM的EDM中，cfSHP1P2和wSHP1P2的中位数分别为3.08 [范围：0 - 163.5] 和9.35 [0.69 - 91.63] ng/ml；不伴有LM的EDM中分别为0 [0 - 0.08] 和0.23 [0 - 7.84] ng/ml；在大多数良性脑膜疾病和伴有LM的非EDM病例中均未检测到。甲基化cfSHP1P2的截断值为0.22 ng/ml，wSHP1P2的截断值为0.59 ng/ml，最有助于鉴别伴有LM的EDM与不伴有LM的EDM（敏感性：79 - 100%；特异性：83 - 100%），以及与其他良性疾病（敏感性：85 - 100%；特异性：78 - 100%）。CSF细胞学检查诊断伴有LM的EDM的敏感性为76%。基于我们的研究，CSF SHP1P2甲基化检测作为伴有LM的EDM辅助诊断工具的作用值得进一步验证。
