Loss of tumor suppressor in lung cancer-1 (TSLC1) expression in meningioma correlates with increased malignancy grade and reduced patient survival

Meningiomas represent the second most common central nervous system tumor affecting adults. Two of the most frequent early events in meningioma tumorigenesis involve loss of expression of the neurofibromatosis 2 (NF2) and 4.1B genes. Recently, 4.1B was shown to interact with the tumor suppressor in lung cancer-1 (TSLC1) protein, prompting us to examine the expression of TSLC1 in meningiomas. We developed specific anti-TSLC1 antibodies to examine TSLC1 expression in normal human leptomeninges, human meningioma cell lines, and human meningiomas of different pathological grades by Western blot (n = 10) and immunohistochemistry (n = 123). Whereas TSLC1 was expressed in normal human leptomeninges by immunohistochemistry, TSLC1 expression was absent in 3 human malignant meningioma cell lines and markedly reduced or absent in 30% of benign meningiomas by Western blot. Restoration of TSLC1 expression in a TSLC1-deficient human meningioma cell line resulted in reduced cell proliferation. In a series of 123 meningiomas (98 adult and 25 pediatric), TSLC1 expression was absent in 48% of benign (WHO grade I), 69% of atypical (grade II), and 85% of anaplastic (grade III) meningiomas. Moreover, TSLC1 loss was associated with decreased patient survival, within the overall group, and in the atypical meningiomas. Collectively, these results suggest that TSLC1 plays an important role in meningioma pathogenesis.