DNA mismatch repair enzyme immunohistochemistry in colorectal cancer: a comparison of biopsy and resection material

Background: Microsatellite instability (MSI) in colorectal cancer (CRC) may be predicted using mismatch repair protein (MMRP) immunohistochemistry (immunostaining), allowing focused genetic investigations and potentially influencing therapeutic interventions. Most laboratories perform immunostaining on surgical resection specimens. Endoscopic biopsy specimens are an alternative tissue source for immunostaining. Given the sensitivity of immunostaining to the degree of tissue fixation, endoscopic biopsy material may produce superior staining, based on faster and more thorough fixation. Moreover, in patients receiving neoadjuvant chemotherapy and/or radiotherapy, endoscopic biopsies may be more useful than surgical resection specimens by allowing assessment of MMR status prior to chemotherapy and/or radiotherapy induced changes in tumours. This study examines whether immunostaining for MMRP expression in CRC is as reliable on endoscopic biopsy material as on surgical resection specimens. Methods: Immunostaining for MLH1, PMS2, MSH2 and MHS6 was performed on 112 unselected CRC cases with both endoscopic biopsy and surgical resection material available. A single observer blindly examined intensity and distribution of staining and assessed MMRP expression. Two consultant histopathologists reviewed challenging cases. Endoscopic biopsies and surgical resections were compared using non-parametric statistical analysis. Results: Immunostaining for all four MMRPs on all 112 cases produced conclusive (i.e., fully interpretable) results in endoscopic biopsies. In surgical resection specimens, 10 stains from nine cases were inconclusive (stains for two MMRPs were inconclusive in one case). In cases where conclusive immunostaining was achieved, there was complete agreement in MMRP status between the endoscopic biopsy and corresponding surgical resection specimens. Overall, MMRP loss was identified in 13% of cases; 11% MLH1, 12% PMS2, 1% MSH2, and 1% MSH6. Immunostaining intensity was significantly higher (p<0.0005) and the distribution of staining was significantly more uniform (p<0.0005) on endoscopic biopsy than on surgical resection. Conclusion: Endoscopic biopsy provides equal accuracy and easier interpretation of MMRP expression immunostaining compared to surgical resection specimens.