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Prognostic impact of β-2-microglobulin expression in colorectal cancers stratified by mismatch repair status
  1. Viktor Hendrik Koelzer1,
  2. Kristi Baker2,
  3. Daniela Kassahn1,
  4. Daniel Baumhoer3,
  5. Inti Zlobec1
  1. 1Institute of Pathology, University of Bern, Bern, Switzerland
  2. 2Department of Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts, USA
  3. 3Institute of Pathology, University Hospital Basel, Basel, Switzerland
  1. Correspondence to: Inti Zlobec, Translational Research, Institute of Pathology, University of Bern, Murtenstrasse 31, Room 414, Bern CH-3010, Switzerland; inti.zlobec{at}


Background β-2-microglobulin (B2M) is essential for antigen presentation, yet may also possess proto-oncogenic properties.

Aim 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.

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