title: Loss of lamin A/C expression in stage II and III colon cancer is associated with disease recurrence.
abstract: OBJECTIVE
  Loss of the nuclear lamina protein lamin A/C (LMNA) has been observed in several human malignancies. The present study aimed to investigate associations between LMNA expression and clinical outcome in colon cancer patients.
  
  
  METHODS
  Clinicopathological data and formalin-fixed paraffin embedded tissues were collected from 370 stage II and III colon cancer patients. Tissue microarrays were constructed, stained for lamin A/C and evaluated microscopically. Microsatellite instability status was determined for 318 tumours.
  
  
  RESULTS
  Low levels of LMNA expression were observed in 17.8% of colon tumours, with disease recurrence occurring in 45.5% of stage II and III colon cancer patients with LMNA-low expressing tumours compared to 29.6% of patients with LMNA-high expressing tumours (p=0.01). For stage II patients, disease recurrence was observed for 35.7% of LMNA-low compared to 20.3% of LMNA-high expressing tumours (p=0.03). Microsatellite stable (MSS) tumours exhibited more frequently low LMNA expression than microsatellite instable (MSI) tumours (21% versus 9.8%; p=0.05). Interestingly, disease recurrence among LMNA-low and LMNA-high expressing MSS tumours varied significantly for stage III patients who had not received adjuvant chemotherapy (100% versus 37.8%; p<0.01) while no such difference was observed for patients who received adjuvant chemotherapy (46.7% versus 46.0%; p=0.96).
  
  
  CONCLUSIONS
  These data indicate that low expression of LMNA is associated with an increased disease recurrence in stage II and III colon cancer patients, and suggest that these patients in particular may benefit from adjuvant chemotherapy.
authors.affiliation: Department of Surgery, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
authors.forename: E J Th
authors.initials: EJ
authors.lastname: Belt
authors.forename: R J A
authors.initials: RJ
authors.lastname: Fijneman
authors.forename: E G
authors.initials: EG
authors.lastname: van den Berg
authors.forename: H
authors.initials: H
authors.lastname: Bril
authors.forename: P M
authors.initials: PM
authors.lastname: Delis-van Diemen
authors.forename: M
authors.initials: M
authors.lastname: Tijssen
authors.forename: H F
authors.initials: HF
authors.lastname: van Essen
authors.forename: E S M
authors.initials: ES
authors.lastname: de Lange-de Klerk
authors.forename: J A M
authors.initials: JA
authors.lastname: Beliën
authors.forename: H B A C
authors.initials: HB
authors.lastname: Stockmann
authors.forename: S
authors.initials: S
authors.lastname: Meijer
authors.forename: G A
authors.initials: GA
authors.lastname: Meijer
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D003110:Colonic Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D034904:Lamin Type A / Q000032:analysis*; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000737:chemistry / Q000175:diagnosis; D009367:Neoplasm Staging; D009426:Netherlands; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D040081:Protein Array Analysis; D012008:Recurrence; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D034904:Lamin Type A; C440308:lamin C