title: SHP-1 promoter 2 methylation in cerebrospinal fluid for diagnosis of leptomeningeal epithelial-derived malignancy (carcinomatous meningitis).
abstract: 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.
authors.affiliation: Department of Medicine, Faculty of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital, Bangkok, 10330, Thailand.
authors.forename: Chanida
authors.initials: C
authors.lastname: Vinayanuwattikun
authors.affiliation: Department of Medicine, Faculty of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital, Bangkok, 10330, Thailand.
authors.forename: Siyamol
authors.initials: S
authors.lastname: Mingmalairak
authors.affiliation: Department of Radiology, Faculty of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital, Bangkok, 10330, Thailand.
authors.forename: Nutchawan
authors.initials: N
authors.lastname: Jittapiromsak
authors.affiliation: Department of Medicine, Faculty of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital, Bangkok, 10330, Thailand.
authors.forename: Iyavut
authors.initials: I
authors.lastname: Thaipisuttikul
authors.affiliation: Department of Medicine, Faculty of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital, Bangkok, 10330, Thailand.
authors.forename: Virote
authors.initials: V
authors.lastname: Sriuranpong
authors.affiliation: Department of Anatomy and Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Faculty of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital, Bangkok, 10330, Thailand.
authors.forename: Apiwat
authors.initials: A
authors.lastname: Mutirangura
authors.affiliation: Department of Pathology and Chulalongkorn GenePRO Center, Faculty of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital, Bangkok, 10330, Thailand. shanop@gmail.com.
authors.forename: Shanop
authors.initials: S
authors.lastname: Shuangshoti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation; D004847:Epithelial Cells / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D055756:Meningeal Carcinomatosis / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging; D008577:Meningeal Neoplasms / Q000134:cerebrospinal fluid / Q000473:pathology; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000134:cerebrospinal fluid* / Q000235:genetics*; D012372:ROC Curve; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6
keywords: Carcinomatous meningitis; Epithelial-derived malignancy; Epithelial-specific methylation marker; Leptomeningeal metastasis; SHP-1 promoter 2 methylation