Clinicopathological features of 50 mismatch repair (MMR)-deficient endometrial carcinomas, tested by immunohistochemistry: A single institutional feasibility study, India

Rekhi, Bharat; Menon, Santosh; Deodhar, Kedar; Ghosh, Jaya; Chopra, Supriya; Maheshwari, Amita

doi:10.1016/j.anndiagpath.2020.151558

Cited by 4 publications

(5 citation statements)

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“…We identified 34 articles studying the prognosis of patients with MMRd tumors in EC [ 25 , 26 , 51 , 54 , 60 , 63 , 70 , 72 , 75 , 76 , 84 , 89 , 92 , 99 , 102 , 105 , 106 , 115 , 120 , 126 , 130 , 131 , 132 , 133 , 135 , 140 , 141 , 153 , 154 , 155 , 156 , 157 , 158 , 159 ]. The studies included an average of 191.5 samples of MMRd tumors (minimum 12, maximum 892).…”

Section: Resultsmentioning

confidence: 99%

“…MMRd tumors were associated with a lower grade EC in three articles [ 106 , 115 , 156 ]; 83% to 90% of low-grade EC tumors had the MMRd phenotype compared with 31.4% to 77% of the MMRp tumor phenotypes. Five articles showed that MMRd tumors were associated with a higher-grade EC [ 25 , 70 , 130 , 132 , 157 ]; 33% of higher-grade tumors were found to be MMRd and associated with endometrioid and mixed histologic tumors.…”

Section: Resultsmentioning

confidence: 99%

“…MMRd tumors were associated with a lower FIGO stage in three articles [ 92 , 106 , 115 ]; 58% to 90% of low-stage EC were MMRd compared with 41.8% to 78% for MMRp tumors. MMRd tumors were associated with higher FIGO stage in six articles [ 25 , 72 , 132 , 135 , 157 , 160 ]; 58% to 66.7% in higher-stage EC were MMRd compared with 17.6% to 40.6% for MMRp tumors.…”

Section: Resultsmentioning

confidence: 99%

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The Role of Immunohistochemistry Markers in Endometrial Cancer with Mismatch Repair Deficiency: A Systematic Review

Favier

Varinot

Uzan

et al. 2022

Cancers

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The objective of this systematic review was to summarize our current knowledge of the role of immunohistochemistry (IHC) markers for identifying mismatch repair-deficient (MMRd) tumors in endometrial cancer (EC). Identification of MMRd tumors, which occur in 13% to 30% of all ECs, has become critical for patients with colorectal and endometrial cancer for therapeutic management, clinical decision making, and prognosis. This review was conducted by two authors applying the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using the following terms: “immunohistochemistry and microsatellite instability endometrial cancer” or “immunohistochemistry and mismatch repair endometrial cancer” or “immunohistochemistry and mismatch repair deficient endometrial cancer”. Among 596 retrieved studies, 161 fulfilled the inclusion criteria. Articles were classified and presented according to their interest for the diagnosis, prognosis, and theragnostics for patients with MMRd EC. We identified 10, 18, and 96 articles using IHC expression of two, three, or four proteins of the MMR system (MLH1, MSH2, MHS6, and PMS2), respectively. MLH1 promoter methylation was analyzed in 57 articles. Thirty-four articles classified MMRd tumors with IHC markers according to their prognosis in terms of recurrence-free survival (RFS), overall survival (OS), stage, grade, and lymph node invasion. Theragnostics were studied in eight articles underlying the important concentration of PD-L1 in MMRd EC. Even though the role of IHC has been challenged, it represents the most common, robust, and cheapest method for diagnosing MMRd tumors in EC and is a valuable tool for exploring novel biotherapies and treatment modalities.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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The Role of Immunohistochemistry Markers in Endometrial Cancer with Mismatch Repair Deficiency: A Systematic Review

Favier

Varinot

Uzan

et al. 2022

Cancers

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“…The annual age-adjusted incidence per 100,000 population in the USA is 7-14 cases, in Australia 17-19 cases, in the Netherlands 5.4-7.1 cases and in Asia 7.4 cases. The median age for occurrence is around 60 years and Cs is marginally more frequent in males [66][67][68][69][70][71]. The elucidation and organizing of the molecular steps that determine the transition from nonmalignant to malignant should allow the stratification of patients according to the distinct pathways that led to carcinoma and provide for new preventive and therapeutic strategies.…”

Section: Discussionmentioning

confidence: 99%

Structural carcinoma overall process: a systematic review

Arabestanino,

Naghibi Irvani,

et al. 2024

Cell. Mol. Biomed. Rep.

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Abnormalities of several oncogenes and tumor suppressor genes have been identified in carcinomas during the last decade and of pathological warfare and physiological traits, and multiple genetic changes have been demonstrated in individual carcinomas. We conducted a systematic review of studies enrolling adolescents and adults with Carcinoma, every type in which a cancer intervention was randomized, or all study designs in which there was a primary or secondary outcome. We searched Ovid MEDLINE, EMBASE, and Evidence-Based Medicine Reviews from 1990 to June 2015. Two reviewers evaluated study eligibility and abstracted data. In total, 67 studies were included and consisted of 62 randomized trials, reviews, and 5 studies. None of the studies (0/81) provided a definition. Only one randomized trial provided a definition. We were unable to identify any definitions used in studies of adolescents and adults with Carcinoma. Given that a proportion of this population may receive intensive treatment, there is an urgent need for consensus-based definitions of use across trials and review systematic and meta-analysis. Article info

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“…Additionally, the broader NEN spectrum includes the neuroendocrine component of gynecological cancers displaying anomalies of MMR genes-proteins [62,63]. A singlecenter study of 104 cases of EC (median age of 53 years) identified 48% (N = 50) with an MMR-deficient status via IHC (N = 33/50: loss of MLH1 and PMS2, N = 14/50: loss of MSH2 and MSH6, N = 2/50: loss of MSH2, N = 1/50 loss of PMS2) and 2/50 of these had focal neuroendocrine differentiation [78]. The first case of NEN at the uterine cervix was reported in 2014 based on a 34-year-old female from a family with LS; the tumor was the first manifestation of the syndrome; small cell neuroendocrine carcinoma was diagnosed; IHC confirmed the loss of MLH1 protein expression [79].…”

Section: Nen and Mmr/msi Assessmentmentioning

confidence: 99%

Pathogenic Insights into DNA Mismatch Repair (MMR) Genes–Proteins and Microsatellite Instability: Focus on Adrenocortical Carcinoma and Beyond

Cârșote

Turturea

Turturea³

et al. 2023

Diagnostics

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DNA damage repair pathways, including mismatch repair (MMR) genes, are prone to carcinoma development in certain patients. The assessment of the MMR system is widely recognized as part of strategies concerning solid tumors (defective MMR cancers), especially MMR proteins (through immunohistochemistry), and molecular assays for microsatellite instability (MSI). We aim to highlight the status of MMR genes–proteins (including MSI) in the relationship with ACC (adrenocortical carcinoma) according to current knowledge. This is a narrative review. We included PubMed-accessed, full-length English papers published between January 2012 and March 2023. We searched studies on ACC patients for whom MMR status was assessed, respectively subjects harboring MMR germline mutations, namely Lynch syndrome (LS), who were diagnosed with ACC. MMR system assessments in ACCs involve a low level of statistical evidence. Generally, there are two main types of endocrine insights: 1. the role of MMR status as a prognostic marker in different endocrine malignancies (including ACC)—which is the topic of the present work, and 2. establishing the indication of immune checkpoint inhibitors (ICPIs) in selective, mostly highly aggressive, non-responsive to standard care forms upon MMR evaluation (which belongs to the larger chapter of immunotherapy in ACCs). Our one-decade, sample-case study (which, to our knowledge, it is the most comprehensive of its kind) identified 11 original articles (from 1 patient to 634 subjects per study diagnosed with either ACC or LS). We identified four studies published in 2013 and 2020 and two in 2021, three cohorts and two retrospective studies (the publication from 2013 includes a retrospective and a cohort distinct section). Among these four studies, patients already confirmed to have LS (N = 643, respective 135) were found to be associated with ACC (N = 3, respective 2), resulting in a prevalence of 0.0046%, with a respective of 1.4% being confirmed (despite not having a large amount of similar data outside these two studies). Studies on ACC patients (N = 364, respective 36 pediatric individuals, and 94 subjects with ACC) showed that 13.7% had different MMR gene anomalies, with a respective of 8.57% (non-germline mutations), while 3.2% had MMR germline mutations (N = 3/94 cases). Two case series included one family, with a respective four persons with LS, and each article introduced one case with LS-ACC. Another five case reports (between 2018 and 2021) revealed an additional five subjects (one case per paper) diagnosed with LS and ACC (female to male ratio of 4 to 1; aged between 44 and 68). Interesting genetic testing involved children with TP53-positive ACC and further MMR anomalies or an MSH2 gene-positive subject with LS with a concurrent germline RET mutation. The first report of LS-ACC referred for PD-1 blockade was published in 2018. Nevertheless, the use of ICPI in ACCs (as similarly seen in metastatic pheochromocytoma) is still limited. Pan-cancer and multi-omics analysis in adults with ACC, in order to classify the candidates for immunotherapy, had heterogeneous results, and integrating an MMR system in this larger and challenging picture is still an open issue. Whether individuals diagnosed with LS should undergo surveillance for ACC has not yet been proven. An assessment of tumor-related MMR/MSI status in ACC might be helpful. Further algorithms for diagnostics and therapy, also taking into consideration innovative biomarkers as MMR-MSI, are necessary.

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Clinicopathological features of 50 mismatch repair (MMR)-deficient endometrial carcinomas, tested by immunohistochemistry: A single institutional feasibility study, India

Cited by 4 publications

References 32 publications

The Role of Immunohistochemistry Markers in Endometrial Cancer with Mismatch Repair Deficiency: A Systematic Review

The Role of Immunohistochemistry Markers in Endometrial Cancer with Mismatch Repair Deficiency: A Systematic Review

Structural carcinoma overall process: a systematic review

Pathogenic Insights into DNA Mismatch Repair (MMR) Genes–Proteins and Microsatellite Instability: Focus on Adrenocortical Carcinoma and Beyond

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