Long-term molecular changes in WHO grade II astrocytomas following radiotherapy

Abstract

Monitoring the long-term radiotherapy-associated molecular changes in low-grade gliomas (LGGs) facilitates the understanding of LGG response to radiotherapy. In this study, we used immunohistochemistry to analyze the expression of Ki-67, tumor protein P53 (TP53), P21, and P27 in 8 paired WHO grade II astrocytoma samples. The interval between radiotherapy (RT) and the second surgery was more than 3 months in all cases. The average Ki-67 labeling index (LI) was 5.3% in pre-RT samples and 11.54% in post-RT samples. Ki-67 LI was higher in the primary tumors that underwent malignant transformation observed at the second surgery after radiation. Post-RT Ki-67 LI decreased in 2 cases with an interval of less than 12 months between RT and the second surgery. TP53 expression was found in 3 out of 4 pre-RT samples with malignant transformation and in 1 out of 4 pre-RT samples without malignant transformation. Post-RT TP53 increased in 2 cases in which increased expression of P21 or P27 was also observed. Our study suggests that radiotherapy can inhibit WHO grade II astrocytoma proliferation as reflected by Ki-67 LI, but the effect attenuates with time. In addition, there is a tendency of malignant transformation for WHO grade II astrocytomas with a high Ki-67 level or TP53 expression in initial samples.

Integrated analysis of inflammatory response subtype-related signature to predict clinical outcomes, immune status and drug targets in lower-grade glioma

“…According to the WHO histopathological grading system, lower-grade gliomas (LGGs) include grade II and III astrocytomas, oligodendrogliomas, and oligoastrocytomas (Brat et al, 2015). Although the prognosis of LGG patients is generally good, the nature of invasiveness and malignant progression makes the treatment of LGG challenging (Yue et al, 2012). Currently, the main treatment for LGG patients consists of surgery followed by radiotherapy and adjuvant chemotherapy.…”

Genetic Alterations of Glioblastoma

“…In proliferating cells, p27 was found in complex with cyclin D/CDK and in G 1 -arrested cells, p27 was bound to cyclin E/CDK2. Very low levels of expression [19] are typical of GBM.…”

Most frequent molecular and immunohistochemical markers present in selected types of brain tumors

“…The crucial role for cell cycle progression seems to depend on the competition for binding of p27 between cyclin D/CDKs and cyclin E/CDK2 complexes. High expression of p27 is present in diffuse astrocytoma (grade II), low expression is seen in malignant gliomas and some carcinomas, and very low expression in anaplastic astrocytomas and glioblastoma (Yue et al 2012).…”