Prostate ductal adenocarcinoma with MLH1 copy number loss, microsatellite instability high and BRCA2 mutation

Mismatch repair deficiency (MMRd) or microsatellite instability high (MSI-H) is rare in prostate cancer and more frequently observed in cases with ductal histology. MLH1 copy number loss is extremely rare in MMRd tumors. Herein, we describe a case of prostate ductal adenocarcinoma with MLH1 copy number loss, microsatellite instability high and BRCA2 mutation could derive benefit from immunotherapy plus ADT. A 72-year-old Chinese patient was diagnosed with poorly differentiated prostate ductal adenocarcinoma mixed with acinar adenocarcinoma (Gleason 5 + 4). Next-generation sequencing (NGS) showed a hypermutated tumor with a mutational burden of 34.71 mutations per Mb and microsatellite instability high (MSI-H). Suspected biallelic MLH1 loss (copy number 0.16) and a pathogenic somatic BRCA2 variant (E2981Kfs*7) were detected. After surgery, the patient received androgen-deprivation therapy (ADT) with goserelin (10.8 mg every 3 months) and tislelizumab (200 mg every 3 weeks). At the 1-year follow-up, the PSA level was lower than 0.01 ng/ml and a pelvic MRI revealed no abnormalities. Our case highlights the intricate molecular mechanisms of MMRd prostate cancer.