In the present study, we explored the diagnostic capability and prognosis of adult brain gliomas according to Nestin expression and its association with clinicopathological characteristics. Nestin is a type VI intermediate filament that is expressed in neural stem cells, cancer stem cells, and poorly differentiated cancer cells. In addition, Nestin contributes to aggressive behaviors, including invasiveness and metastasis, in various tumors. These studies raised the question of whether Nestin can act as a prognostic marker for high-grade gliomas, and previous studies have examined its viability as a potential marker for glioma stem cells. However, the results of studies focusing on different populations were inconclusive. To date, there is no study considering the correlation of IDH mutation and the new WHO classification.
Our study showed no relationship between Nestin expression and patient sex; however, an older age was associated with stronger Nestin expression. High-grade gliomas, specifically glioblastomas, are common in the elderly. Although, gliomas located in the frontal lobe tend not to express Nestin, as such expression is no longer present after differentiation into mature neural cells. Considering that adult neural stem cells are located in the subventricular zone, fully-differentiated glial cells and glial tumor cells in the cortex can be expected not to express Nestin. Higher-grade gliomas are mainly developed in the deep portion and in continuity with the lateral ventricle.
Diffuse astrocytoma, oligodendroglioma, and anaplastic oligodendroglioma showed no strong expression of Nestin in IHC. Less than half of diffuse astrocytoma (42.8%, 6/14), anaplastic oligodendroglioma (46.2%, 6/13), and a case of oligodendroglioma (6.7 %, 1/15) weakly highlighted Nestin expression. Anaplastic astrocytoma showed weak Nestin-positivity in more than half (57.1% in IDH-mutant, 66.7% in IDH-wild) and strong positivity in each case. All glioblastomas with wild-type IDH demonstrated strong Nestin expression. Both the expression rate and intensity of Nestin tended to increase with the degree of WHO grade. However, Nestin expression was negatively correlated with IDH mutation. Given these results, Nestin expression and intensity were significantly correlated with pathologic diagnosis. In daily clinical practice, IHC for Nestin could be very useful for pathologic diagnosis. Difficulty in conducting the biopsy of brain parenchymal lesions and small amount of biopsy specimens contributed to diagnostic challenges. Moreover, differentiating glioblastomas from other gliomas is very difficult if the specimen has no necrosis or microvascular proliferation. In our analysis, all glioblastomas, IDH-wildtype, showed strong Nestin expression. Considering expression and intensity of Nestin at the time of diagnosis, glioblastomas will not be overlooked. Nestin could be a useful marker for diagnosis. This result concurs with that of previous studies (21–23).
Nestin has been associated with cell growth, migration, invasion, and adhesion to the extracellular matrix. Therefore, gliomas with strong Nestin expression are expected to have a poor prognosis (24), while other studies have shown that Nestin expression has an effect on prognosis in some subgroups of patients or showed no relationship with prognosis (12, 25, 26). In our study, patients with Nestin-positive tumors had significantly worse survival than those without Nestin expression, regardless of clinicopathological characteristics. In terms of prognostic utility, Nestin expression was found to be comparable to IDH mutation status. The multivariate analysis for the survival of patients with brain glioma according to clinicopathological parameters revealed that Nestin expression is a significant molecular marker, independent of IDH mutation.
In this study, we used IHC for Nestin in brain gliomas to verify its feasibility as a diagnostic and prognostic marker in new WHO classification, independent of IDH mutation. Nestin expression has a negative prognostic effect and serves as an independent marker of survival. Clear correlation between the expression rate and intensity of Nestin and pathologic diagnosis makes an accurate patient diagnosis.