Clinical significance of mismatch repair gene expression in sporadic colorectal cancer

Abstract

Mismatch repair (MMR) genes play an important role in the occurrence and development of sporadic colorectal cancer; however, the effect of MMR genes on clinicopathological features and prognosis remains unclear. The aim of the present study was to observe the clinical significance of MMR gene expression in sporadic colorectal cancer. Clinicopathological data and postoperative samples from 404 patients with sporadic colorectal cancer were obtained from the Affiliated Tumor Hospital of Xinjiang Medical University. The immunohistochemistry PV-9000 two-step method was performed to measure the protein expression of human mutL homolog 1 (hMLH1), human mutS homolog (hMSH) 2, human postmeiotic segregation increased 2 (hPSM2) and hMSH6. Differences in clinicopathological features, family history and survival time subsequent to surgery between groups with normal and aberrant MMR protein (MMRP) expression were compared. A total of 27.23% of all patients showed aberrant nuclear staining of MMRP. Among the patients with aberrant MMRP expression, a higher proportion of patients showed aberrant expression of more than one type of MMRP than aberrant expression of only one type of MMRP. Aberrant expression of hMLH1/hPSM2 was most commonly observed (29/404). In addition, aberrant MMRP expression in colorectal cancer was indicated predominantly in the right hemicolon. Histological type primarily showed mucinous adenocarcinoma. In addition, with increasing body mass index (BMI), the MMRP deficiency rate was also shown to increase gradually. There was a close association between MMRP expression deficiency and family history of cancer (P<0.05). For TNM stage III patients, the Kaplan-Meier survival curve showed that the aberrant MMRP expression group had a three-year disease-free survival (DFS) rate of 66.67%, which was longer than the DFS rate of the normal group (55.41%), with no statistical difference (P>0.05). In conclusion, the immunohistochemistry PV-9000 two-step method can be used to measure MMRP expression in colorectal cancer. Aberrant MMRP expression is closely correlated with tumor location, histological type, BMI and tumor family history in sporadic colorectal cancer. Aberrant MMRP expression may have an effect on the prognosis of stage III patients.

Keywords: clinicopathological parameters; immunohistochemistry; mismatch repair genes; prognosis; sporadic colorectal cancer.

Figure 1

Immunohistochemical staining showing normal and aberrant MMRP expression (magnification, ×100). (A) hMLH1, (B) hMSH2, (C) hPMS2 and (D) hMSH6. (Aa-Da) Normal immunohistochemical staining of (Aa) hMLH1, (Ba) hMSH2, (Ca) hPMS2 and (Da) hMSH6. Normal nuclear staining of the MMRPs can be observed not only in stromal cells, but also in epithelial tumor cells, showing a brownish accumulation of dye in the nucleus. (Ab-Db) Aberrant staining of (Aa) hMLH1, (Ba) hMSH2, (Ca) hPMS2 and (Da) hMSH6. Aberrant nuclear staining of the MMRPs can only be observed in stromal cells, not in epithelial tumor cells. MMRP, mismatch repair protein; hMLH1, human mutL homolog 1; hMSH, human mutS homolog; hPMS2, human postmeiotic segregation increased 2.

Figure 2

Survival comparison between normal and aberrant MMRP expression groups. The three-year DFS rate was 58.65%, of which 20 cases showed aberrant expression of MMRP. The aberrant MMRP expression group had a three-year DFS rate of 66.67%; this was higher than that of the normal group, which had a three-year DFS rate of 55.41%, but no statistical difference was observed (P>0.05). Censored values were calculated due to events such as unrelated mortality. MMRP, mismatch repair protein; DFS, disease-free survival.