Markers of cell division cycle in glioblastoma: significance in prediction of treatment response and patient prognosis. (December 2013)

• Record Type: Journal Article
• Authors: Yousaf, J.; Hills, C.; Dixit, S.; Achawal, S.; O'Brien, D.; Greenman, J.; Scott, I. S.
• Is Part Of: British journal of neurosurgery. Volume 27:Number 6(2013:Dec.)
• Page Start: 752
• Page End: 758
• Publication Date: 2013-12
• Subjects: Nervous system -- Surgery -- Periodicals; 617.48
• DOI: 10.3109/02688697.2013.773287
• Languages: English
• ISSNs: 0268-8697

Abstract

<abstract> <title>Abstract</title> <p> <italic>Objective.</italic> 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. <italic>Method.</italic> 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. <italic>Results.</italic> 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. <italic>Conclusions.</italic> 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<sup>6</sup>MGMT expression and 1p;19q deletion status.</p> </abstract>