Commonly encountered difficulties in MMR protein immunohistochemistry interpretation
| Interpretation difficulty | Comment |
| Weak MMR protein staining throughout the tumour and in stromal and inflammatory cells (internal controls) | Compare staining in tumour cells to that within internal controls. If both compartments are weak this is likely to be technical for example, poor antigen preservation. Be cautious before diagnosing dMMR in this situation |
| Absent MMR protein staining in the tumour and internal controls | This is most likely to be technical failure but in the appropriate clinical context also consider the possibility of ‘constitutional MMR deficiency’ |
| Patchy loss of MMR protein staining in the tumour | Compare staining in tumour cells to that within internal controls. If both compartments are weak this is likely to be technical but if the internal controls are well stained in the same area then this is likely to be due to a clonal genetic event affecting the corresponding MMR gene |
| Cytoplasmic MMR protein expression within tumour | This can occur when an MMR gene mutation is present and the abnormal protein accumulates within the cytoplasm |
dMMR, deficient MMR; MMR, mismatch repair.