Discordant mismatch repair status between colon and rectal adenocarcinomas in a single patient: a case report

Colorectal cancer (CRC) is the most common malignant tumor of the digestive tract, with steadily increasing annual incidence and mortality rates. Mismatch repair (MMR) status and microsatellite instability (MSI) are critical biomarkers for the diagnosis and management of CRC. MSI-high (MSI-H) tumors show significant responsiveness to immune checkpoint inhibitors. A 78-year-old man presented to our hospital with an 8-month history of intermittent epigastric discomfort. Imaging and endoscopy revealed a colonic tumor infiltrating the adjacent gastric wall with local perforation. Immunohistochemical analysis of an endoscopic biopsy confirmed adenocarcinoma with loss of MLH1 and PMS2 expression, but retained MSH2 and MSH6 expression. PCR-based MSI testing indicated MSI-H status. After 22 months of tislelizumab treatment (30 cycles administered every 3 weeks), the patient experienced substantial abdominal pain relief, with only sporadic mild discomfort. Follow-up imaging and endoscopy 6 months after treatment identified rectal adenocarcinoma expressing all four MMR proteins, and MSI PCR confirmed microsatellite stability (MSS), with no further differentiation between primary and metastatic lesions performed. The patient subsequently received three cycles of CAPOX chemotherapy (capecitabine and oxaliplatin) combined with tislelizumab but refused further treatment. Currently, the patient reports only mild epigastric discomfort without impairment of daily activities. This case documents discordant MMR status between tumors at two distinct anatomical sites, the colon and rectum, in the same patient, highlighting the clinical importance of reassessing MMR/MSI status in newly diagnosed or clinically progressive lesions, particularly when therapeutic responses differ across tumor sites.