Overexpression of c-erbB2 is a negative prognostic factor in anaplastic astrocytomas

The epidermal growth factor receptor (EGFR) family, consisting of four tyrosine kinase receptors, c-erbB1-4, seems to be influential in gliomagenesis. The aim of this study was to investigate EGFR gene amplification and expression of c-erbB1-4 receptor proteins in human anaplastic astrocytomas. Formalin-fixed and paraffin-embedded sections from 31 cases were investigated by standard immunohistochemical procedures for expression of c-erbB1-4 receptor proteins using commercial antibodies. EGFR gene amplification was studied by fluorescence in situ hybridization using paraffin-embedded tissues. Two monoclonal antibodies, NCL-EGFR-384 and NCL-EGFR, were used for EGFR detection and they displayed positive immunoreactivity in 97% and 71%, respectively. For c-erbB2 detection three monoclonal antibodies, CB11, 3B5, and 5A2, were applied and they displayed positive immunoreactivity in 45%, 100%, and 52%, respectively. Positive immunostaining for c-erbB3 and c-erbB4 was encountered in 97% and 74%, respectively. The EGFR gene was amplified in 9 out of 31 tumors (29%). After adjusting for age, Karnofsky performance status, and extent of surgical resection, Cox multiple regression analysis with overall survival as the dependent variable revealed that c-erbB2 overexpression detected by the monoclonal antibody clone CB11 was a statistically significant poor prognostic factor (P = 0.004). This study shows the convenience and feasibility of immunohistochemistry when determining the expression of receptor proteins in tissue sections of human astrocytomas. The synchronous overexpression of c-erbB1-4 proteins in anaplastic astrocytomas supports their role in the pathogenesis of these tumors. Further, c-erbB2 overexpression seems to predict aggressive behaviour

Evaluation of the proliferation markers Ki-67/MIB-1, mitosin, survivin, pHH3, and DNA topoisomerase IIα in human anaplastic astrocytomas - an immunohistochemical study

<p>Abstract</p> <p>Background</p> <p>Histological malignancy grading of astrocytomas can be challenging despite criteria given by the World Health Organisation (WHO). Grading is fundamental for optimal prognostication and treatment, and additional biomarkers are needed to support the histopathological diagnosis. Estimation of proliferative activity has gained much enthusiasm, and the present study was designed to evaluate and compare novel immunohistochemical proliferative markers in human anaplastic astrocytomas.</p> <p>Methods</p> <p>Proliferative activity was determined in twenty-seven cases with antibodies reactive against the Ki-67 antigen, mitosin, survivin, pHH3, and DNA topoisomerase IIα, and they were mutually compared as well as related to mitotic activity.</p> <p>Results</p> <p>The markers correlated well with each other, but poorly with mitoses, probably because of small and squeezed tumour samples, in which identification of mitoses can be difficult. Positive association to overall survival was observed as well.</p> <p>Conclusions</p> <p>Our data show that these markers may assist significantly in the evaluation of proliferative activity in anaplastic astrocytomas and even have prognostic value.</p

DNA topoisomerase IIα and mitosin expression predict meningioma recurrence better than histopathological grade and MIB-1 after initial surgery.

BACKGROUND:The 2016 WHO histopathological grade or conventional biomarker MIB-1 is insufficient for predicting meningioma recurrence after initial treatment and alternative strategies are required. In this study, we investigated whether DNA topoisomerase IIα and/or mitosin expression can predict tumor recurrence with greater accuracy than conventional methods. METHODS:The expression of MIB-1, topoisomerase IIα, and mitosin were determined as proliferation indices in tissue microarrays using immunohistochemistry. The accuracy of prognostication was assessed with receiver operating characteristic (ROC) analyses and standard survival analyses. RESULTS:Expression of topoisomerase IIα and mitosin was significantly higher in recurrent meningioma than in non-recurrent meningioma (P ≤ 0.031), but no difference in MIB-1 expression was observed (P = 0.854). ROC analysis found topoisomerase IIα and mitosin expression to be the most reliable predictors of recurrence compared to WHO histopathological grade and MIB-1 expression. This result was supported by the multivariate survival analysis, in which mitosin expression was a significant predictor of recurrence-free survival (P < 0.001) and no association was found with histopathological grade or MIB-1 expression (P ≥ 0.158). CONCLUSIONS:The results suggest that topoisomerase IIα and mitosin improve prognostication of patients resected for meningioma. Tumors with higher topoisomerase IIα and/or mitosin expression have a higher risk of recurrence after initial treatment, and these patients may benefit from adjuvant treatment and closer radiological follow-up

Kaplan-Meier plot of survivin labeling index (LI) < 1% vs. > 1%.

<p>Patients with survivin LI > 1% had significant shorter recurrence-free survival compared to patients with survivin LI < 1%.</p

Clinical data according to 2016 WHO histopathological grade.

<p>Clinical data according to 2016 WHO histopathological grade.</p

Comparisons of labelling indices.

<p>Comparisons of labelling indices.</p

Cox hazard univariate and multivariate survival analyses of proliferation assessment methods for recurrence-free survival.

<p>Cox hazard univariate and multivariate survival analyses of proliferation assessment methods for recurrence-free survival.</p