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.

Association between Microsatellite Instability Status and Peri-Operative Release of Circulating Tumour Cells in Colorectal Cancer

“…As is well established in the literature, MSI-H CRCs are also associated with poor differentiation [19,37], are larger and more likely to be mucinous [38][39][40], as well as being higher grade tumours with a greater mutational burden and the mucinous phenotype more likely to be associated with signet cells. It is also believed that MSI-H CRCs are associated with a high number of frameshift mutation peptides (FSPs) [41,42] when compared to MSS CRCs [43,44]. The MSI hyper-mutational state is also thought to be the reason for poor differentiation and other adverse pathological features of the tumour.…”

The correlation between DNA mismatch repair status and the clinicopathological and molecular features of Chinese sporadic colorectal cancer

“…Similarly, Yoon et al ( 11 ) evaluated 2,028 tumour samples, and found that MSI-high tumours were typically larger. However, both Sun et al ( 12 ) and Faghani et al ( 13 ) have reported that there was no significant relationship between tumour size and MMR status. Interestingly, the MMR system can activate cell-cycle checkpoints or apoptosis, which might partially explain the occurrence of over-proliferation in tumours with defective MMR.…”

Prognostic Value of Mismatch Repair Genes for Patients With Colorectal Cancer: Meta-Analysis

“… 11 - 13 , 24 , 26 Four studies showed longer DFS in the patients with CRC with deficient hMLH1 or hMSH2. 14 - 16 , 28 However, Bendardaf et al suggested that deficient MMR demonstrated a shorter DFS. This inconsistency could be explained by combining with other genes (TS) and distinctive clinic features indicating that CRC with deficient MMR is apt to display marked peritumoral and intratumoral lymphocytic infiltration.…”