Prognostic marker analysis in pediatric intracranial ependymomas.

Histologic grading methods dependent upon H&E staining review have not been shown to reliably predict survival in children with intracranial ependymomas due to the subjectivity of the analytical methods. We hypothesized that the immunohistochemical detection of MIB-1, Tenascin C, CD34, VEGF, and CA IX may represent objective markers of post-operative survival (Progression Free and Overall Survival; PFS, OS) in these patients. Intracranial ependymomas from patients aged 22 years or less were studied. The original histologic grade was recorded, H&E sections were reviewed for vascular proliferation status, and immunohistochemistry was used to determine MIB-1, Tenascin C, CD34, VEGF, and CA IX status. Based upon the World Health Organization (WHO) grading system, 3 Grade I, 18 Grade II and 9 Grade III ependymomas were studied. Median follow-up time was 9.0 years; median PFS was, 6.1 years. Original WHO grade did not correlate with PFS or OS. Peri-necrotic CA IX localization correlated with PFS (Log rank = 0.0181) and OS (Log rank p = 0.0015). All patients with a CA IX ≤ 5 % total area localization were alive at last follow-up. Perinecrotic CA IX staining was also associated with vascular proliferation (p = 0.006), though not with VEGF expression score. MIB-1 labeling index (LI) correlated with OS (HR 1.06, 95 % CI 1.01, 1.12) and PFS (HR 1.08, 95 % CI 1.02, 1.14). MIB-1 LI and perinecrotic CA IX individually correlated with PFS. The effect of perinecrotic CA IX remained when grade was added to a Cox model predicting PFS. Immunodetection of CA IX and MIB-1 expression are predictive biomarkers for survival in children with posterior fossa ependymomas. These markers represent objective indicators of survival that supplement H&E grading alone.

Overexpression of SOX11 and TFE3 in Solid-Pseudopapillary Neoplasms of the Pancreas.

OBJECTIVES: To characterize the expression of SOX11 and TFE3 proteins in solid-pseudopapillary neoplasms (SPNs) and their histologic mimickers. METHODS: Immunohistochemistry for SOX11, TFE3, and ß-catenin was performed on 31 cases of surgically resected SPNs. Neuroendocrine tumors, acinar cell carcinomas, and pancreatoblastomas served as controls. RESULTS: Nuclear immunoreactivity for SOX11 was detected in all SPNs and five of 31 control tumors. Nuclear immunoreactivity for TFE3 was detected in 30 SPNs and three control tumors. Nuclear immunoreactivity for ß-catenin was detected in all SPNs and four control tumors. The combination of three markers as immunohistochemical panels resulted in optimal sensitivity and specificity. CONCLUSIONS: Both SOX11 and TFE3 were overexpressed in SPNs and may be involved in the pathogenesis. Clinically, SOX11 and TFE3 can be potentially used as diagnostic markers in distinguishing indeterminate SPNs from their histologic mimickers.