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Chinese Archives of General Surgery(Electronic Edition) ›› 2022, Vol. 16 ›› Issue (02): 116-121. doi: 10.3877/cma.j.issn.1674-0793.2022.02.006

• Original Article • Previous Articles     Next Articles

Significance of mismatched repair protein expression loss in colorectal cancer

Guoju Shen1,(), Daiwen Wang1, Chuan Peng2, Xiaofeng Si1, Jiayi Xu1   

  1. 1. Department of Pathology, Panzhihua City Central Hospital, Panzhihua 617000, China
    2. Department of Radiology, Panzhihua City Integrated Traditional Chinese and Western Medicine Hospital, Panzhihua 617000, China
  • Received:2021-11-15 Online:2022-04-01 Published:2022-04-19
  • Contact: Guoju Shen

Abstract:

Objective

To detect the expression of mismatch repair (MMR) protein in colorectal cancer, and to explore the correlation between deficient mismatch repair (dMMR) and clinicopathological features and its impact on the prognosis of patients.

Methods

The clinical data and pathological tissue samples of 214 patients with colorectal cancer undergoing radical surgery in Panzhihua City Central Hospital from January 2019 to May 2021 were collected retrospectively. Immunohistochemical staining and Western blotting were used to detect the expression of MMR proteins (hMSH2, hMSH6, hMLH1 and hPMS2) in clinical tumor tissues and corresponding adjacent normal tissues respectively, and the loss of any protein expression was determined as dMMR. The correlation between MMR protein expression and clinicopathological features was analyzed. Pearson correlation analysis was used to test the correlation between the loss of expression of four MMR proteins in colorectal cancer. Kaplan-Meier survival curve was drawn to analyze the influence of dMMR on the prognosis and survival of patients.

Results

(1) The positive staining of the four MMR proteins were mainly distributed in the nucleus, showing brownish yellow or brown signals. dMMR was found in 33 (15.4%) of 214 colorectal cancer patients, which was significantly higher than 3.3% (7/214) of the corresponding adjacent normal tissues, and the difference was statistically significant (χ2=18.642, P<0.001). HMLH1 protein expression was lost in 25 cases, hPMS2 in 20 cases, hMSH2 in 12 cases and hMSH6 in 9 cases. MMR proteins were often co-expressed deletion, mainly in hMLH1/hPMS2. (2) dMMR was associated with tumor location, which was more common in the right colon cancer patients. And proficiency of MMR (pMMR) patients were more likely to be located in the rectum and left colon, presenting as high-medium differentiated adenocarcinoma. The loss of hMLH1 expression was mostly in medium-low differentiated adenocarcinoma, which was closely related to tumor diameter, degree of differentiation and TNM stage. The loss of hMSH2 expression was closely related to tumor diameter, while the loss of hPMS2 expression to the degree of differentiation, TNM stage and the depth of muscular invasion, and the loss of hMSH6 expression to tumor morphology (all P<0.05). (3) There was positive correlation between the expression loss of four MMR proteins in colorectal cancer tissues, and the co-expression deletion of hMLH1/hPMS2 and hMSH2/hMSH6 were the most significant (P<0.05). (4) The cumulative overall survival rate of dMMR patients was 84.8%, which was significantly higher than that of pMMR patients (61.3%), and the difference was statistically significant (Log-rank χ2=2.985, P=0.043).

Conclusions

The incidence of dMMR in colorectal cancer tissues is higher than that in normal adjacent tissues, the proportion of dMMR is higher in the right colon cancer patients, and the co-expression deletion of hMLH1/hPMS2 is more common. dMMR is closely related to the clinicopathological features of patients, and the prognosis may be better, which has important guiding significance for the judgment of clinical malignant degree of colorectal cancer, the selection of treatment plan, and the prediction of prognosis of patients.

Key words: Colorectal neoplasms, Mismatch repair protein, Expression deletion, Pathological features, Prognosis

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