Immunohistochemical analysis of cyclin A in astrocytic tumours

Abstract

Cyclins are important regulators of the cell cycle; there is increasing evidence that some cyclins are positively involved in carcinogenesis. Amplification and translocation of the cyclin genes and overexpression of their mRNAs and proteins have been observed in a variety of tumours. We studied cyclin A protein in astrocytic tumours by immunohistochemical analysis. Immunohistochemistry with microwave antigen retrieval was carried out on formalin fixed, paraffin embedded material from 15 glioblastomas (WHO grade IV), 10 anaplastic astrocytomas (WHO grade III), seven diffuse low grade astrocytomas (WHO grade II) and nine pilocytic astrocytomas (WHO grade I) using antibodies against cyclin A and a proliferation marker MIB1. Staining for these antibodies was seen mainly in the tumour cell nuclei; 66% of all cases showing staining for cyclin A and 95% of all cases staining for MIB1. Mean labelling indices (LI) for cyclin a were higher in glioblastoma (mean LI-6.7) and anaplastic astrocytoma (mean LI-5.9) than low grade diffuse astrocytoma (mean LI-1.7) and pilocytic astrocytoma (mean LI-0.12), although there was no clear cut off point between the various tumour types. A good correlation was seen between labelling indices of cyclin A and MIB1 (Pearson correlation coefficient r = 0.59, P < 0.0001). Cyclin A is variably expressed in astrocytic tumours, either reflecting increased tumour proliferation (cyclin A being an integral component of the cell cycle), an alteration of its gene, protein upregulation or regulation of apoptosis. The genetic basis of expression of cyclin A in astrocytic tumours remains to be determined.

Immunohistochemical estimation of cell cycle entry and phase distribution in astrocytomas: applications in diagnostic neuropathology

“…Frequency of cyclin A expression has been found to be associated with increasing grade of astrocytoma in a previous study [38], with very similar LIs to the findings we describe. On the other hand, we found all tumours in our study to express cyclin A, regardless of histology or grade, compared to expression in only 66% of cases in the previous study [38]. It is possible that technical and/or other limitations in the previous study were responsible for the observation that 34% of gliomas appeared to have no cells in S‐phase of the cell cycle.…”

“…Previous investigations have shown a correlation between outcome in glial tumours and expression of individual cell cycle markers such as Ki67, cyclin D1 and cyclin A [36–40]. Indeed, Mcm‐2 has been shown previously to provide prognostic information in a small series of oligodendrogliomas [27].…”

Expression of cyclin A and topoisomerase IIα of oligodendrogliomas is correlated with tumour grade, MIB‐1 labelling index and survival

“…Over‐expression or deregulated expression of cyclins A and B can contribute to the development of neoplastic disorders, either directly or indirectly by causing the phosphorylation of oncogenic products by a cyclin‐dependent kinase 27 . In brain tumours, there have been several studies about cyclin A in astrocytic tumours, 8,9 but in oligodendrogliomas, none was found in an extensive Medline search. In our study, we found that cyclin A played an important role in malignant transformation of this tumour and the LI of cyclin A in low‐grade oligodendrogliomas and high‐grade oligodendrogliomas was 1.18 ± 0.98 versus 4.65 ± 1.99, respectively.…”

“…Several studies concerning various cyclins in non‐oligodendroglial glial tumours 8,9 and the usefulness of Ki67 in oligodendrogliomas 10–14 have been reported. However, only a couple of studies of cyclin A and cyclin D in oligodendroglioma can be found in a Medline search 15,16 .…”

Molecular neuro-oncology and the development of targeted therapeutic strategies for brain tumors Part 5: apoptosis and cell cycle

“…Expression of cyclins and Cdks are frequently increased in high-grade astrocytomas, often through amplification of gene dosage [122,166,[168][169][170][171][172][173]. However, these alterations are uncommon in low-grade gliomas, such as pilocytic astrocytomas [174].…”