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Br J Neurosurg. 2013 Dec;27(6):752-8. doi: 10.3109/02688697.2013.773287. Epub 2013 Mar 11.

Markers of cell division cycle in glioblastoma: significance in prediction of treatment response and patient prognosis.

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  • 1Departments of Neurosurgery, Hull & East Yorkshire Hospitals NHS Trust , Hull Royal Infirmary, Hull , UK.

Abstract

OBJECTIVE:

To investigate whether expression of regulatory components of the cell division cycle can be used independently to predict survival and response to adjuvant therapy in glioblastomas.

METHOD:

A tissue micro-array, constructed using glioblastomas (n = 66), was stained using antibodies against minichromosome maintenance protein-2 (Mcm-2), expressed throughout the cell-division cycle; geminin, a protein that prevents re-initiation of DNA replication; and cyclin A, an S-phase cyclin. A semi-quantitative labelling index (LI) was calculated using an average of 18 high-power fields (hpf) in three replicate cores. The patients were divided into two groups: Group 1 (n = 50) underwent surgery and radiotherapy with 24 patients receiving temozolomide, and Group 2 (n = 16) received surgical treatment only.

RESULTS:

The LIs (median +/- IQR) for Group 1 were as follows: Mcm-2, 36.7% (22.9%-51.8%); geminin, 7.8% (5.8%-10.5%); and cyclin A, 4.2% (2.4%-6.9%). Elevated LIs, higher than the median, for geminin and cyclin A correlated with prolonged survival when the tumours received adjuvant therapy (Kaplan-Meier curves, p = 0.0046 and p = 0.0063 for geminin and cyclin A, respectively). Linear regression analysis revealed positive correlations with survival for Mcm-2 (p = 0.0376), geminin (p = 0.0006) and cyclin A (p = 0.004). In Group 2, there was no relationship between the patient survival and the LI for any marker.

CONCLUSIONS:

Geminin and cyclin A, each show potential as independent prognostic markers in glioblastomas receiving adjuvant therapy. This may reflect the fact that both geminin and cyclin A estimate proliferating tumour cell subpopulations sensitive to radio/chemotherapy. These markers could provide valuable prognostic information, even in small biopsies, especially if combined with O(6)MGMT expression and 1p;19q deletion status.

PMID:
23477614
[PubMed - indexed for MEDLINE]
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