Figure 5.

The presence of a TP53‐mutation is an important prognostic feature in SHH‐activated medulloblastomas. A typical wild‐type tumor is depicted in panels A‐D. The tumor demonstrates the typical pattern of immunoreactivity for YAP1 and GAB1 (B and C, respectively). Immunoreactivity for p53 restricted to weak expression in the minority of tumor cells in TP53‐wild‐type tumors (D). A tumor from a patient with Li‐Fraumeni syndrome is shown in panels E‐H. SHH‐activated, TP53‐mutant tumors often show large cell/anaplastic histology (E). This case demonstrates the typical immunophenotype of a SHH‐activated tumor with immunoreactivity for YAP1 and GAB1 (F and G). Strong, diffuse immunoreactivity for p53 is present (H) indicative of a dominant‐negative TP53‐mutation. Because many SHH‐activated tumors with TP53 mutations are associated with germline TP53 mutations, genetic testing is recommended for all cases showing a mutant pattern.