Mismatch repair-deficient status associates with favorable prognosis of Eastern Chinese population with sporadic colorectal cancer

Abstract

The present study aimed to investigate the expression level of DNA mismatch repair gene (MMR) in in sporadic colorectal cancer (SCRC) in eastern China, and to investigate the association between MMR status and prognosis of patients with SCRC. Patient archives from the Department of Gastrointestinal Surgery of Weihai Municipal Hospital (Weihai, China) were retrospectively collected between January 2011 and January 2012. Of the 221 consecutive patients identified, 192 patients who met the criterion were deemed eligible for inclusion. Immunohistochemistry (IHC) was conducted to detect the expression of MMR proteins MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MSH6 and PMS1 homolog 2, mismatch repair system component (PMS2) expression and mutation in sporadic colorectal cancer (SCRC). Kaplan-Meier plots and log-rank tests were performed to conduct survival analysis and Cox proportional hazard regression models were conducted to determine independent prognostic factors. The total rate of deficient MMR (dMMR) was 14.58% (28/192): MSH6, 0.52% (1/192); PMS2, 4.17% (8/192); MSH2/MSH6, 3.65% (7/192); and MLH1/PMS2, 6.25% (12/192). The dMMR group had a significantly longer overall survival time compared with proficient MMR (pMMR) group (P=0.017). Disease-free survival time of dMMR group was also longer than pMMR group (P=0.027). Multivariate analysis using the Cox regression model confirmed that MMR status was an independent prognostic factor for SCRC. Loss of MMR expression was indicative of a favorable outcome for patients with SCRC, and MMR status could be viewed as an independent prognostic factor.

The Prognostic Value of Deficient Mismatch Repair in Stage II–IVa Nasopharyngeal Carcinoma in the Era of IMRT

“…The expression of MMR proteins and the rate of dMMR were variable in different cancers or variable according to interpretation criteria [24][25][26][27][28][29][30] . Previous studies reported that 14.6-26.0% of patients in colorectal cancer 24,25 and 16.0-45.0% in endometrial cancer [26][27][28][29][30] were dMMR, 3.7-6.0% of patients in colorectal cancer 24,25 and 0.0-4.2% in endometrial cancer [26][27][28][29][30] showed the simultaneous loss of MSH2 and MSH6, 78.4-89.6% of patients in colorectal cancer 24,25 and 70.2-92.6% in endometrial cancer [26][27][28][29][30] showed MLH1/PMS2-double preserved, and 3.9-4.2% of patients in colorectal cancer 24,25 and 0.5-4.9% in endometrial cancer [26][27][28][29][30] showed the loss of PMS2 alone. Some studies have demonstrated that normal expression is defined as the presence of the nuclear staining of tumour cells regardless of the proportion or intensity [25][26][27][28][29][30][31][32] .…”

“…Some studies have demonstrated that normal expression is defined as the presence of the nuclear staining of tumour cells regardless of the proportion or intensity [25][26][27][28][29][30][31][32] . However, other researchers believe that the intensity of staining and the proportion of positive cells must be considered comprehensively 17,23,24,33 . The latter approach was used in our study, and the proportion of NPC patients with dMMR was 49.3%, which was higher than the proportion in two previous reports (approximately 2%) 10,11 on NPC.…”

“…Misrepair of radiation -induced DNA damage underlies genomic instability and increased radiosensitivity 36 ; thus, MMR-defective cells may underlie increased radiosensitivity. www.nature.com/scientificreports www.nature.com/scientificreports/ Previous studies have reported that compared with patients with pMMR tumours, colorectal cancer patients with dMMR tumours had significantly superior OS and PFS 24,37 , and endometrial cancer patients with dMMR tumours had significantly superior PFS 38 . In this study, there was no significant difference (P > 0.05) between the dMMR and pMMR groups in sex, age, clinical stage, T category, N category or therapy regimens.…”

Biomarkers for precision immunotherapy in the metastatic setting: hope or reality?

“…Next-generation sequencing (NGS) with higher sensitivity is also being used to detect MSI in various malignancies [ 86 ]. In colorectal [ 87 ], ovarian [ 88 ], endometrial [ 89 ] and GC [ 90 ], MMR malfunction/MSI is reported as a prognostic biomarker. Contrary, it has been shown that in breast cancer, IHC and MSI testing are not interchangeable tests meaning that each type of cancer requires different and optimised management [ 8 , 91 ].…”

Prognostic and predictive role of DNA mismatch repair status in stage II‐III colorectal cancer: A systematic review and meta‐analysis

“…9 It has long been recognized that patients with dMMR cancers tend to have a better prognosis than patient with proficient MMR (pMMR). [10][11][12][13][14] However, individual studies failed to demonstrate the association between MMR status and overall survival (OS) or diseasefree survival (DFS) among stage I-IV CRC patients 15 or stage II-III CRC patients. 16,17 Conflicting results were also seen in meta-analysis.…”