Immunohistochemical study of mismatch repair and programmed death ligand-1 protein expression in prostatic acinar adenocarcinoma in correlation with patient clinicopathological parameters

Abstract

Background Castrate-resistant prostate cancer (CRPC) is the main challenge among prostate cancer patients; most are metastatic and eventually resist any treatment. No cure yet exists for them. Aim Investigate the immunohistochemical expression of mismatch repair genes (MMR) protein products for loss of expression and programmed death ligand-1 (PDL-1) overexpression in prostatic acinar adenocarcinoma cases as a trial to find benefit from using immune checkpoint inhibitor drugs as a new therapeutic modality, especially in CRPC. Patients and methods This study included 166 cases of prostatic acinar adenocarcinoma of different grades and stages along with different responses to therapy including 57% being classified as CRPC. Tissue microarray was applied using mostly three cores from each donor case, resulting in the formation of six new recipient blocks. Immunohistochemical staining for MSH2, MSH6, MLH1, PMS2, and PDL-1 was done. Interpretation of the results, their correlation with all collected clinical and pathological parameters, and statistical analysis of the results were done. Results Most of the studied cases showed retained nuclear stain for all MMR genes (MSH2, MSH6, MLH1, PMS2), with total loss of the nuclear stain found in few cases ranging from one (0.7%) case in MLH1 to six (4.2%) cases in MSH2. PDL-1 was expressed in about seven (4.8%) cases. No significant correlation was found between MMR protein loss or PDL-1 expression and the different clinicopathological parameters including CRPC. Conclusion The limited cases that showed MMR protein loss or PDL-1 expression may suggest that the immune checkpoint inhibitors are of limited value in CRPC but can be used as the last option after investigations of these markers as still few cases can show these changes. Patchy loss of MMR proteins is suggested to be further investigated by molecular studies.