title: Prognostic impact of β-2-microglobulin expression in colorectal cancers stratified by mismatch repair status.
abstract: BACKGROUND
  β-2-microglobulin (B2M) is essential for antigen presentation, yet may also possess proto-oncogenic properties.
  
  
  OBJECTIVE
  To determine the prognostic impact of B2M in patients with mismatch repair (MMR) proficient and deficient colorectal cancer (CRC) and to investigate whether this effect on outcome is dependent on the local immune response.
  
  
  METHODS
  B2M protein expression and tumour-infiltrating immune cells (CD3, CD16, CD163, CD20, CD4, CD45RO, CD56, CD68, CD8, FoxP3, GranzymeB, iNOS, mast cell tryptase, MUM1, PD1, TIA-1) were evaluated in a well characterised tissue microarray of 408 CRCs. The predictive value for clinicopathological features and the prognostic significance of B2M expression were analysed, stratified by MMR status and the immunohistological characteristics of immune cell infiltrates.
  
  
  RESULTS
  Interobserver agreement for B2M staining was high (intra-class correlation coefficient=0.91). Complete B2M loss was more frequent in MMR-deficient (19.4%) compared to MMR-proficient (7.1%) tumours (p<0.001). In MMR-deficient cases, B2M loss predicted rare local recurrence (p=0.034), infrequent nodal-positivity (p=0.035), absence of distant metastasis (p=0.048; sensitivity=100%) and a trend towards favourable survival (p=0.124) independent of immune infiltrates. No associations between B2M and clinicopathological features were observed in MMR-proficient cases.
  
  
  CONCLUSIONS
  Our data show for the first time that absence of B2M protein expression identifies MMR-deficient cancers with a favourable clinical course and absence of metastatic disease. Validation of B2M protein expression for sub-classification of MMR-deficient CRC is recommended for future clinical trials.
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Viktor Hendrik
authors.initials: VH
authors.lastname: Koelzer
authors.forename: Kristi
authors.initials: K
authors.lastname: Baker
authors.forename: Daniela
authors.initials: D
authors.lastname: Kassahn
authors.forename: Daniel
authors.initials: D
authors.lastname: Baumhoer
authors.forename: Inti
authors.initials: I
authors.lastname: Zlobec
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D053843:DNA Mismatch Repair / Q000235:genetics*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D015996:Survival Rate; D013557:Switzerland / Q000453:epidemiology; D046888:Tissue Array Analysis; D001613:beta 2-Microglobulin / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D001613:beta 2-Microglobulin