Loss of MSH2 protein expression is a risk factor in early stage cervical cancer

Nijhuis, E., Nijman, H., Oien, K., Bell, A., Ten Hoor, K., Reesink-Peters, N., Boezen, H., Hollema, H. and van der Zee, A. (2007) Loss of MSH2 protein expression is a risk factor in early stage cervical cancer. Journal of Clinical Pathology, 60(7), pp. 824-830. (doi: 10.1136/jcp.2005.036038)

Abstract

Background: Loss of mismatch repair (MMR) gene expression has been associated with fewer metastases and improved prognosis in various tumour types. Aims: To evaluate the predictive and prognostic significance of loss of MMR protein MSH2 in early stage cervical cancer. Methods: Specimens from 218 consecutive patients with early stage, surgically treated cervical cancer were analysed. Median age was 42 years (interquartile range 35 - 53). International Federation of Gynecology and Obstetrics (FIGO) stages were IB1 (57%), IB2 (25%) and IIA (18%). Histology was 70% squamous cell, 6% adenosquamous and 24% adenocarcinoma. Pelvic lymph node metastasis was present in 66 (30%) patients. Median follow-up was 5.2 years (interquartile range 2.5 - 7.9). Tissue microarrays (TMAs) were constructed containing three cores of paraffin-embedded tumour per case. MSH2 expression was assessed by immunohistochemistry on TMAs and full sections. Results: In TMAs MSH2 expression could be analysed in 184/218 (84%) tumours. Loss of MSH2 was observed in 58/184 (32%) tumours, with a moderately strong concordance between TMAs and full sections (kappa = 0.47). In tumours with loss of MSH2, pelvic lymph node metastasis and cancer invasion beyond 10 mm were more frequent (48% vs 25%, and 59% vs 37%, respectively). However, loss of MSH2 expression was not related to recurrence or survival. Conclusion: TMAs are powerful tools for high throughput screening of biological markers for prognostic value in cervical cancer. Absence of MSH2 expression is associated with a high-risk profile in early stage cervical cancer, but does not predict lymph node status with sufficient accuracy to be used in the clinic.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Oien, Professor Karin
• Authors: Nijhuis, E., Nijman, H., Oien, K., Bell, A., Ten Hoor, K., Reesink-Peters, N., Boezen, H., Hollema, H., and van der Zee, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Clinical Pathology
• Publisher: BMJ Publishing Group Ltd.
• ISSN: 0021-9746