MSI testing

Rüschoff, Josef; Baretton, Gustavo; Bläker, Hendrik; Dietmaier, Wolfgang; Dietel, Manfred; Hartmann, Arndt; Horn, Lars‐Christian; Jöhrens, Korinna; Kirchner, Thomas; Knüchel, Ruth; Mayr, Doris; Merkelbach‐Bruse, Sabine; Schildhaus, Hans–Ulrich; Schirmacher, Peter; Tiemann, Markus; Tiemann, Katharina; Weichert, Wilko; Büttner, Reinhard

doi:10.1007/s00292-021-00948-3

Cited by 13 publications

(7 citation statements)

References 47 publications

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“…Although patients with MSI-H/dMMR constitute a limited proportion of CRC patients, it is likely that the number of patients with MSI-H/dMMR CRC will increase with the rising number of cases of CRC, both in China and elsewhere ( 1 , 2 , 33 , 34 ). For these patients, clinical studies suggest that they could gain considerable benefit from treatment with ICIs because MSI-H/dMMR tumors are highly infiltrated by immune cells, which show dramatic responses to several ICIs ( 35 ).…”

Section: Discussionmentioning

confidence: 99%

The cost-effectiveness analysis of serplulimab versus regorafenib for treating previously treated unresectable or metastatic microsatellite instability-high or deficient mismatch repair colorectal cancer in China

Zhou

et al. 2023

Front. Oncol.

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ObjectiveThe aim of this study was to investigate the cost-effectiveness of serplulimab versus regorafenib in previously treated unresectable or metastatic microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) colorectal cancer in China.MethodsFrom the perspective of China’s health-care system, a Markov model with three health states (progression free, progression, death) was developed for estimating the costs and health outcomes of serplulimab and regorafenib. Data for unanchored matching-adjusted indirect comparison (MAIC), standard parametric survival analysis, the mixed cure model, and transition probabilities calculation were obtained from clinical trials (ASTRUM-010 and CONCUR). Health-care resource utilization and costs were derived from government-published data and expert interviews. Utilities used to calculate quality-adjusted life years (QALYs) were obtained from clinical trials and literature reviews. The primary outcome was the incremental cost-effectiveness ratio (ICER) expressed as cost/QALY gained. Four scenarios were considered in scenario analysis: (a) using original survival data without conducting MAIC; (b) limiting the time horizon to the follow-up time of the clinical trial of serplulimab; (c) adopting a fourfold increase in the risk of death; and (d) applying utilities from two other sources. One-way sensitivity analysis and probabilistic sensitivity analysis were also performed to assess the uncertainty of the results.ResultsIn the base-case analysis, serplulimab provided 6.00 QALYs at a cost of $68,722, whereas regorafenib provided 0.69 QALYs at a cost of $40,106. Compared with that for treatment with regorafenib, the ICER for treatment with serplulimab was $5,386/QALY, which was significantly lower than the triple GDP per capita of China in 2021 ($30,036), which was the threshold used to define the cost-effectiveness. In the scenario analysis, the ICERs were $6,369/QALY, $20,613/QALY, $6,037/QALY, $4,783/QALY, and $6,167/QALY, respectively. In the probabilistic sensitivity analysis, the probability of serplulimab being cost-effective was 100% at the threshold of $30,036/QALY.ConclusionCompared with regorafenib, serplulimab is a cost-effective treatment for patients with previously treated unresectable or metastatic MSI-H/dMMR colorectal cancer in China.

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Section: Discussionmentioning

confidence: 99%

The cost-effectiveness analysis of serplulimab versus regorafenib for treating previously treated unresectable or metastatic microsatellite instability-high or deficient mismatch repair colorectal cancer in China

Zhou

et al. 2023

Front. Oncol.

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“…This is closely associated with drug resistance in cancer treatment, which greatly limits the effectiveness of cancer therapy. As a result, we examined the correlation between GLS and three significant ITH indicators in pan-cancer, namely “Tumor Mutation Burden” (TMB) [ 48 ], “Microsatellite Instability” (MSI) [ 49 ] and “Homologous Recombination Deficiency” (HRD) [ 50 ]. The simple nucleotide variation dataset was acquired from TCGA [ 51 ], and TMB/MSI/HRD values for each cancer were calculated using the Sangerbox database [ 41 ] with the same established parameters.…”

Section: Methodsmentioning

confidence: 99%

A paradigm shift in cancer research based on integrative multi-omics approaches: glutaminase serves as a pioneering cuproptosis-related gene in pan-cancer

Shi,

Mugaanyi,

et al. 2024

BMC Women's Health

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Background Cuproptosis is a newly identified form of unprogrammed cell death. As a pivotal metabolic regulator, glutaminase (GLS) has recently been discovered to be linked to cuproptosis. Despite this discovery, the oncogenic functions and mechanisms of GLS in various cancers are still not fully understood. Methods In this study, a comprehensive omics analysis was performed to investigate the differential expression levels, diagnostic and prognostic potential, correlation with tumor immune infiltration, genetic alterations, and drug sensitivity of GLS across multiple malignancies. Results Our findings revealed unique expression patterns of GLS across various cancer types and molecular subtypes of carcinomas, underscoring its pivotal role primarily in energy and nutrition metabolism. Additionally, GLS showed remarkable diagnostic and prognostic performance in specific cancers, suggesting its potential as a promising biomarker for cancer detection and prognosis. Furthermore, we focused on uterine corpus endometrial carcinoma (UCEC) and developed a novel prognostic model associated with GLS, indicating a close correlation between GLS and UCEC. Moreover, our exploration into immune infiltration, genetic heterogeneity, tumor stemness, and drug sensitivity provided novel insights and directions for future research and laid the foundation for high-quality verification. Conclusion Collectively, our study is the first comprehensive investigation of the biological and clinical significance of GLS in pan-cancer. In our study, GLS was identified as a promising biomarker for UCEC, providing valuable evidence and a potential target for anti-tumor therapy. Overall, our findings shed light on the multifaceted functions of GLS in cancer and offer new avenues for further research.

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“…Assessment of MMRd via immunohistochemistry or MSI-H via different molecular pathologic approaches to detect microsatellite instability are standard techniques in surgical and molecular pathology for decades. 54 Detection of MSI-H status is most commonly performed using the Bethesda consensus panel consisting of the well-known 3 dinucleotides (D2S123, D17S250, and D5S346) and 2 mononucleotides (BAT25 and BAT26). 55 Based on the approval, both the immunohistochemical detection of an MMRd and the molecular pathologic detection of an MSI-H status are sufficient for pembrolizumab therapy.…”

Section: The Role Of the Programmed Cell Death Protein 1 And Programm...mentioning

confidence: 99%

“…Although these rates are overall low, patients without treatment options might benefit from a MMRd/MSI-H status assessment. Assessment of MMRd via immunohistochemistry or MSI-H via different molecular pathologic approaches to detect microsatellite instability are standard techniques in surgical and molecular pathology for decades 54. Detection of MSI-H status is most commonly performed using the Bethesda consensus panel consisting of the well-known 3 dinucleotides (D2S123, D17S250, and D5S346) and 2 mononucleotides (BAT25 and BAT26) 55.…”

Section: The Role Of the Programmed Cell Death Protein 1 And Programm...mentioning

confidence: 99%

Immunotherapy in Genitourinary Cancers: Role of Surgical Pathologist for Detection of Immunooncologic Predictive Factors

Bahlinger

Hartmann

Eckstein

2022

Advances in Anatomic Pathology

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Genitourinary malignancies include a broad spectrum of distinct tumor entities occurring in the kidney, the urinary tract, the prostate, the adrenal glands, the penis, and testicles. Each tumor entity presents with unique biological characteristics, especially in terms of immunobiology. The immune landscape of genitourinary malignancies differs between immunoreactive tumors like urothelial carcinoma or carcinomas of the kidney, for which several immunotherapeutic treatment options have been approved in the past years. In contrast, prostate cancer presents with low immunogenicity and previous trials exploring immune checkpoint inhibitors and other immunotherapeutic agents did not proof substantial survival benefits. In this review, we are presenting a streamlined overview on the role of surgical pathologists within the contemporary practice of immune oncology. It includes current indications for pathologic programmed death-ligand 1 (PD-L1) assessment and important pathologic considerations on PD-L1 testing harmonization including interassay and algorithm variabilities. In addition, we will discuss emerging biomarkers beyond PD-L1 and their potential to predict immunotherapy responses including tumor mutational burden, microsatellite instability, gene expression signatures, and histologic factors.

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MSI testing

Cited by 13 publications

References 47 publications

The cost-effectiveness analysis of serplulimab versus regorafenib for treating previously treated unresectable or metastatic microsatellite instability-high or deficient mismatch repair colorectal cancer in China

The cost-effectiveness analysis of serplulimab versus regorafenib for treating previously treated unresectable or metastatic microsatellite instability-high or deficient mismatch repair colorectal cancer in China

A paradigm shift in cancer research based on integrative multi-omics approaches: glutaminase serves as a pioneering cuproptosis-related gene in pan-cancer

Immunotherapy in Genitourinary Cancers: Role of Surgical Pathologist for Detection of Immunooncologic Predictive Factors

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