An Unusual Immunohistochemical “Null” Pattern of Four MMRs Proteins of Gastric Cancer and Literature Review

Abstract Background: Immunohistochemical (IHC) stainings for the mismatch repair (MMR) proteins are useful methods for the treatment and prognosis in gastric cancer. Different IHC staining patterns reflect the complex biological phenomena underlying MMR deficiency. We herein report a rare IHC staining pattern of four MMR-related proteins in gastric cancer.Case presentation: An “null” IHC staining pattern of four MMR-related proteins in a 67–year-old man with gastric cancer, including MLH1, PMS2, MSH2, and MSH6. The results remained unchanged after repeated tests. We find the promoter hypermethylation of MLH1 subsequently. Moreover, next-generation sequencing showed that the four genes exhibited changes. One of these was the somatic mutation of the missing copy number in exon 14 of MSH2. Mutation analysis using peripheral blood showed no germline mutation in the these four genes. The patient had no personal or family tumor history. After finishing the above work, we classified this case as sporadic case. The patient returned to normal after the operation. 9 months after operation, patients were admitted to hospital and no signs of tumor metastasis and recurrence were found. After 6 cycles of adjuvant chemotherapy, the patients and was discharged home in a stable condition.Conclusions: It is greatly important for the patient and their relatives to improve the understanding of abnormal IHC findings and the biological significance by clinicians. This observation revealed a rare but potential phenomenon in assessing MMR proteins, and explained this was a sporadic case that needed no clinical management implications for his family.