Diagnostic and prognostic significance of cyclin A expression in low-grade astrocytomas: comparison with astrogliosis and high-grade tumors

Abstract

Aim: Definitive distinction between low-grade astrocytoma and astrogliosis is a long-standing difficulty, due to their similar histopathological characteristics. To clarify differences in biological significance, we focused on various components of the cell cycle machinery and proliferation as key parameters, comparing expression in astrogliosis as well as low- and high-grade astrocytomas.

Methods: The expression of p16, p21, and p27, cyclins A, cyclin D1, cyclin E, Rb, and Ki-67 was immunohistochemically examined in 40 cases of astrogliosis and 48 of low-grade astrocytomas (Grade II), as well as 50 high-grade tumors (Grade III and IV). The results were also compared with survival data for the astrocytomas.

Results: Cell proliferation determined by Ki-67 immunoreactivity did not differ between astrogliosis and low-grade tumors. Average labelling indices (LIs) for p16, p21, Rb, cyclin A, and cyclin E showed stepwise increase from astrogliosis, through low- to high-grade astrocytomas, indicating the possibility that over 9%, 6% and 4% of LIs for p16, p21 and cyclin A, respectively, may be useful predictors for the latter, in contrast to significant decrease in p27 LIs. Significantly higher values for cyclin D1 were also evident in astrogliosis as compared to astrocytomas. Positive correlations between LIs for Rb and Ki-67 were observed with astrogliosis and low- but not high-grade tumors. In addition, high cyclin A LI values were independently associated with poor outcome in low-grade tumors.

Conclusion: These findings provide evidence that expression of cell cycle-related molecules may be a reliable parameter for differential diagnosis of low-grade astrocytomas and astrogliosis. Moreover, detection of cyclin A appears to be useful for predicting behavior of low-grade astrocytomas.