title: Loss of MSH2 protein expression is a risk factor in early stage cervical cancer.
abstract: BACKGROUND
  Loss of mismatch repair (MMR) gene expression has been associated with fewer metastases and improved prognosis in various tumour types.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gynecological Oncology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: E R
authors.initials: ER
authors.lastname: Nijhuis
authors.forename: H W
authors.initials: HW
authors.lastname: Nijman
authors.forename: K A
authors.initials: KA
authors.lastname: Oien
authors.forename: A
authors.initials: A
authors.lastname: Bell
authors.forename: K A
authors.initials: KA
authors.lastname: ten Hoor
authors.forename: N
authors.initials: N
authors.lastname: Reesink-Peters
authors.forename: H M
authors.initials: HM
authors.lastname: Boezen
authors.forename: H
authors.initials: H
authors.lastname: Hollema
authors.forename: A G J
authors.initials: AG
authors.lastname: van der Zee
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D053842:Microsatellite Instability; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D040081:Protein Array Analysis / Q000379:methods; D012307:Risk Factors; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein