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Claudin‐6 is of Limited Sensitivity and Specificity for the Diagnosis of Atypical Teratoid/Rhabdoid Tumors

Recent gene expression microarray analyses have indicated that claudin‐6 is specifically expressed in atypical teratoid rhabdoid tumors (AT/RTs), suggesting a role as a positive diagnostic marker in addition to SMARCB1 (INI1) loss, which is encountered in the majority of AT/RTs. In order to investigate the potential of claudin‐6 as a diagnostic marker, expression was investigated in 59 AT/RTs and 60 other primary central nervous system (CNS) tumors, including primitive neuroectodermal tumors, medulloblastomas, choroid plexus tumors, and both pediatric and adult low‐ and high‐grade gliomas using immunohistochemistry. Claudin‐6 was expressed in 17/59 AT/RTs (29%), but also in a variety of other primary CNS tumors, including 60% of medulloblastomas and 21% of malignant gliomas. Even though high staining scores (2+ or 3+) were more often encountered in AT/RTs (Chi‐square 4.177; P = 0.041), the overall frequency of claudin‐6 staining was not significantly higher in AT/RTs as compared with the other tumors (17/59 vs. 16/60; Chi‐square = 0.328; P = 0.567). In a subgroup of 43 AT/RT patients, of which follow‐up data were available, claudin‐6 expression did not show any correlation with survival. In conclusion, claudin‐6 immunohistochemistry is of limited sensitivity and specificity for the diagnosis of AT/RT and does not correlate with clinical behavior.