Clinicopathological features of mismatch repair protein expression patterns in colorectal cancer

Chow, Nan Haw; Chen, Yi Lin; Ho, Chung Liang; Yeh, Yu Min; Lin, Shao Chieh; Lin, Peng; Lin, Bo; Chu, Chien An; Tsai, Hung Wen; Lee, Jenq Chang

doi:10.1016/j.prp.2020.153288

Cited by 15 publications

(7 citation statements)

References 27 publications

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“…Second, this study is a single-center, retrospective, so the level of evidence-based medicine is not high enough. Third, the tumor characteristics of patients in this study were inconsistent with those reported in other large-sample study ( 37 ). For example, the proportion of BRAF mutations in this study was relatively low, while the proportion of isolated MSH2 loss was relatively high, about 20%.…”

Section: Discussioncontrasting

confidence: 92%

Efficacy and Safety of Neoadjuvant Monoimmunotherapy With PD-1 Inhibitor for dMMR/MSI⁃H Locally Advanced Colorectal Cancer: A Single-Center Real-World Study

Zhang

Yang

et al. 2022

Front. Immunol.

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ObjectiveTo explore the efficacy and safety of single-agent programmed cell death protein-1 (PD-1) inhibitor in the neoadjuvant treatment of patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) locally advanced colorectal cancer (LACRC) through single-center large⁃sample analysis based on real⁃world data in China.MethodsThis study was a retrospective, single-center, case series study. 33 colorectal cancer (CRC) patients with clinical stage of T3~4N0~2M0 treated in Yunnan Cancer Hospital from June 2019 to June 2021 were analyzed retrospectively. Among them, 32 patients were dMMR or MSI-H or both dMMR and MSI-H, and one patient was both dMMR and microsatellite stability (MSS) (excluded in the final analysis). All 32 patients received neoadjuvant immunotherapy (nIT) with single-agent PD⁃1 inhibitor.ResultsAmong the 32 patients, 8 (25%) were locally advanced rectal cancer (LARC) and 24 (75%) were locally advanced colon cancer (LACC); 4 (12.55%) were stage II and 28 (87.5%) were stage III. The median number of cycles of 32 patients with dMMR/MSI-H LACRC receiving nIT with single-agent PD-1 blockade was 6 (4~10), and the median number of cycles to achieve partial response (PR) was 3 (2~4). Among them, three LARC patients achieved clinical complete response (cCR) and adopted the watch-and-wait (W&W) strategy. The objective response rate (ORR) of the other 29 patients with radical surgery was 100% (29/29), the pathological response rate was 100% (29/29), the rate of major pathological response (MPR) was 86.2% (25/29), and the rate of pathological complete response (pCR) was 75.9% (22/29). The incidence of immune-related adverse events (irAEs) in 32 patients during nIT was 37.5% (12/32), while the incidence of irAEs in 22 patients with operation during adjuvant immunotherapy was 27.3% (6/22), all of which were grade 1~2. No grade 3 or above irAEs were occured. The median time from the last nIT to surgery was 27 (16~42) days. There were no delayed radical resection due to irAEs in these patients. All 29 patients achieved R0 resection. The incidence of surgical-related adverse events (srAEs) in perioperative period was 10.3% (3/29).ConclusionsNeoadjuvant monoimmunotherapy with PD-1 inhibitor has favorable ORR and pCR rate, and relatively low incidences of irAEs and srAEs for patients with dMMR/MSI-H LACRC, suggesting that this nIT regimen of single-agent PD-1 inhibitor is significantly effective and sufficiently safe.

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Section: Discussioncontrasting

confidence: 92%

Efficacy and Safety of Neoadjuvant Monoimmunotherapy With PD-1 Inhibitor for dMMR/MSI⁃H Locally Advanced Colorectal Cancer: A Single-Center Real-World Study

Zhang

Yang

et al. 2022

Front. Immunol.

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“…Loss of MLH1 and PMS2 expression is the most common dMMR IHC pattern. 27 In our study, this was found to be less frequent than deficiency in both MSH2 and MSH6 although this may not be significant due to the small sample size. A similar observation was reported by Jung et al, surmising that a lower incidence of the MLH1/ PMS2-deficient IHC pattern was due to false-positive cases.…”

Section: Discussioncontrasting

confidence: 57%

Clinicopathologic Factors Associated with Mismatch Repair Status Among Filipino Patients with Young-Onset Colorectal Cancer

Sacdalan¹,

Garcia²,

Diwa³

et al. 2021

CMAR

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“…In total, 30 peri-tumorous specimens were replaced by blood of the same individuals. Protocol of the PCR reactions followed that described previously [ 28 ]. The PCR products were analysed through capillary electrophoresis using the QIAxcel DNA screening kit and Advanced System ( Qiagen GmbH, Hilden, Germany) according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

High concordance rate of capillary electrophoresis workflow for microsatellite instability analysis and mismatch repair (MMR) immunostaining in colorectal carcinoma

Huang

Lee

et al. 2023

PLoS ONE

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Microsatellite instability (MSI) is the primary predictive biomarker for therapeutic efficacies of cancer immunotherapies. Establishment of the MSI detection methods with high sensitivity and accessibility is important. Because MSI is mainly caused by defects in DNA mismatch repair (MMR), immunohistochemical (IHC) staining for the MMR proteins has been widely employed to predict the responses to immunotherapies. Thus, due to the high sensitivity of PCR, the MSI-PCR analysis has also been recommended as the primary approach as MMR IHC. This study aimed to develop a sensitive and convenient platform for daily MSI-PCR services. The routine workflow used a non-labeling QIAxcel capillary electrophoresis system which did not need the fluorescence labeling of the DNA products or usage of a multi-color fluorescence reader. Furthermore, the 15 and 1000 bp size alignment markers were used to precisely detect the size of the DNA product. A cohort of 336 CRC cases was examined by MSI-PCR on the five mononucleotide MSI markers recommended by ESMO. The PCR products were analyzed in the screening gels, followed by high-resolution gel electrophoresis for confirmation if needed. In the MSI-PCR tests, 90.1% (303/336) cases showed clear major shift patterns in the screening gels, and only 33 cases had to be re-examined using the high-resolution gels. The cohort was also analyzed by MMR IHC is, which revealed 98.5% (331/336) concordance with MSI-PCR. In the five discordant cases, 4 (3 MSI-L and 1 MSS) showed MSH6 loss. Besides, one case exhibited MSI-H but no loss in the MMR IHC. Further NGS analysis, in this case, found that missense and frameshift mutations in the PMS2 and MSH6 genes occurred, respectively. In conclusion, the non-labeling MSI-PCR capillary electrophoresis revealed high concordance with the MMR IHC analysis and is cost- and time-effective. Therefore, it shall be highly applicable in clinical laboratories.

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Clinicopathological features of mismatch repair protein expression patterns in colorectal cancer

Cited by 15 publications

References 27 publications

Efficacy and Safety of Neoadjuvant Monoimmunotherapy With PD-1 Inhibitor for dMMR/MSI⁃H Locally Advanced Colorectal Cancer: A Single-Center Real-World Study

Efficacy and Safety of Neoadjuvant Monoimmunotherapy With PD-1 Inhibitor for dMMR/MSI⁃H Locally Advanced Colorectal Cancer: A Single-Center Real-World Study

Clinicopathologic Factors Associated with Mismatch Repair Status Among Filipino Patients with Young-Onset Colorectal Cancer

High concordance rate of capillary electrophoresis workflow for microsatellite instability analysis and mismatch repair (MMR) immunostaining in colorectal carcinoma

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