ORIGINAL ARTICLE

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

E R Nijhuis¹, H W Nijman¹, K A Oien⁴, A Bell⁵, K A ten Hoor¹, N Reesink-Peters¹, H M Boezen³, H Hollema², A G J van der Zee¹

¹ Department of Gynecological Oncology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
² Department of Pathology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
³ Department of Epidemiology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
⁴ Department of Pathology, University of Glasgow, Glasgow, UK
⁵ Department of Pathology, Western Infirmary, Glasgow, UK

Correspondence to:
Correspondence to:
Dr A G J van der Zee
Department of Gynaecologic Oncology, University Medical Centre Groningen, PO Box 30.001, 9700 RB Groningen, the Netherlands; a.g.j.van.der.zee{at}og.umcg.nl

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 ( = 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.

Abbreviations: DFS, disease-free survival; FIGO, International Federation of Gynecology and Obstetrics; HNPCC, hereditary non-polyposis colorectal carcinoma; LNM, lymph node metastasis; LOH, loss of heterozygosity; LVSI, lymph vascular space involvement; MMR, mismatch repair; MSI, microrosatellite instability; NCI, National Cancer Institute; OR, odds ratio; OS, overall survival; RFS, recurrence-free survival; RT, radiation therapy; TMA, tissue microarray

Keywords: uterine cervical neoplasms; tissue microarray; prognostic marker; MSH2 protein; human

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