Usefulness of immunohistochemistry for mismatch repair protein and microsatellite instability examination in adenocarcinoma and background endometrium of sporadic endometrial cancer cases

Saeki, Harumi; Hlaing, May Thinzar; Horimoto, Yoshiya; Kajino, Kazunori; Ohtsuji, Naomi; Fujino, Keiji; Terao, Yasuhisa; Hino, Okio

doi:10.1111/jog.14061

Cited by 12 publications

(11 citation statements)

References 27 publications

(39 reference statements)

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“…Furthermore, no relationship had been observed between the MSI status and the estrogen (ER) status and the International Federation of Gynecology and Obstetrics (FIGO) stage. However, there was a significant relationship between MSI-H and the loss of MMR proteins (27). In the present study, the lack of expression of at least one protein was reported in 12% of the patients, which had a similar pattern to that illustrated in Saeki et al (27).…”

Section: Discussionsupporting

confidence: 81%

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Prevalence of DNA Mismatch Repair Deficiency in Endometrial Cancer Using Immunohistochemistry

et al. 2022

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Background: Endometrial cancer (EC) is known as the most common malignancy of the female reproductive system, suggested to be associated with hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome (LS). Objectives: Therefore, the aim of the present study was to screen for LS in patients with EC using immunohistochemistry (IHC). Methods: In this retrospective cross-sectional study, the patients with EC, referred to Qaem Hospital, Mashhad, Iran, from 2015 - 2019, were enrolled. Paraffin-embedded tissue blocks were then examined via IHC for the expression of four mismatch repair (MMR) proteins, including MLH1, MSH2, MSH6, and PMS2. The demographic and tumor-related data were also extracted from medical records and pathology reports. The data were consequently analyzed at the significance level of P < 0.05. Results: A total number of 100 patients with EC were evaluated using IHC, and 12 (12%) cases were found suspected. As well, no significant relationship was observed between LS and age, tumor site, tumor histology, tumor size, tumor grade, tumor-infiltrating lymphocytes (TILs), and a family/personal history of malignancies. Conclusions: The prevalence of LS based on the IHC expression of the MMR proteins (MLH1, MSH2, MSH6, and PMS2) was 12% in the patients with EC. There was also no significant relationship between the cases suspected and the demographic and tumor-related data.

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Section: Discussionsupporting

confidence: 81%

“…However, there was a significant relationship between MSI-H and the loss of MMR proteins (27). In the present study, the lack of expression of at least one protein was reported in 12% of the patients, which had a similar pattern to that illustrated in Saeki et al (27).…”

Section: Discussionsupporting

confidence: 81%

Prevalence of DNA Mismatch Repair Deficiency in Endometrial Cancer Using Immunohistochemistry

et al. 2022

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“…The comparative analysis between these methods showed some discrepancies; in particular, approximately 1–68% of dMMR-IHC cases were MSS by PCR/NGS [ 83 , 86 , 144 , 145 , 146 ], and about 5% of pMMR-IHC cases were MSI-H by molecular analysis [ 147 , 148 ].…”

Section: Msi In Gynecologic Cancersmentioning

confidence: 99%

Microsatellite Instability: From the Implementation of the Detection to a Prognostic and Predictive Role in Cancers

Amato

Franco

Facchini

et al. 2022

IJMS

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Microsatellite instability (MSI) has been identified in several tumors arising from either germline or somatic aberration. The presence of MSI in cancer predicts the sensitivity to immune checkpoint inhibitors (ICIs), particularly PD1/PD-L1 inhibitors. To date, the predictive role of MSI is currently used in the selection of colorectal cancer patients for immunotherapy; moreover, the expansion of clinical trials into other cancer types may elucidate the predictive value of MSI for non-colorectal tumors. In clinical practice, several assays are used for MSI testing, including immunohistochemistry (IHC), polymerase chain reaction (PCR) and next-generation sequencing (NGS). In this review, we provide an overview of MSI in various cancer types, highlighting its potential predictive/prognostic role and the clinical trials performed. Finally, we focus on the comparison data between the different assays used to detect MSI in clinical practice.

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“…Loss of the MLH1-PMS2 heterodimer ranges from 5.78-26.92% of cases while loss of the MSH2-MSH6 heterodimer ranges from 4.1-9.72%. Isolated MSH6 has been reported in 1.98-6.48% of cases while isolated PMS2 loss is less common at 0.14-1.45% of cases [13][14][15][16][17][18][19][20][21]. Complete loss of all four proteins is rare, with only a handful of cases reported in published literature.…”

Section: Introductionmentioning

confidence: 99%

Mismatch Repair Protein Expression Defects in Endometrioid Endometrial Adenocarcinoma

Brincat¹

2020

Preprint

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Objectives: Endometrioid endometrial carcinoma (EEC) is the sentinel cancer in over half female patients with heritable mismatch repair (MMR) mutations as part of Lynch syndrome. Immunohistochemical testing for tumoural MMR-protein expression is the primary screening test identifying cases potentially harbouring familial cancer syndrome-related mutations and is also a predictive biomarker for immune-checkpoint blockade response. Methods: Following Data Protection and Ethical clearance by the University of Malta, 200 EEC cases were retrospectively identified and categorized into three arms: 151 cases above age 50 at diagnosis, 49 cases at or below age 50 at diagnosis and 30 controls with benign endometrial tissue sampling. H&E case slides were re-examined by an independent pathologist to confirm the diagnosis and identify the block best representing the tumour. Four new slides per case were recut and immunohistochemistry performed for MLH1, PMS2, MSH2, and MSH6 proteins. Protein expression was analysed semiquantitatively using Allred scoring. Results: 31% of the overall EEC cases were deficient for one or more MMR-proteins. Dual loss of the MLH1-PMS2 protein heterodimer was the most common deficiency, occurring in 24.5% of cases. Loss of MSH2-MSH6 protein expression represented 3.2% of MMR-deficient cases. Well di ferentiated tumours had a 76.5% proficiency rate as opposed to grade 2/3 disease with 53.2% and 52.9% proficiency rate respectively. There was no significant di ference in MMR status when age 50 was used as a hypothetical testing threshold. A ter correcting for tumour grade, MLH1 and PMS2 expression was shown to be negatively correlated with age-at-diagnosis while MSH6 expression was positively correlated. Conclusion: Re lex MMR proficiency testing of all EEC cases is advisable, as using age 50 as a testing threshold would have missed 82.3% of MMR deficient cases. Prospective evidence is required to clarify the role semi-quantitative scoring plays in MMR status interpretation and patient management in the ever-evolving field of targeted therapeutics.

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Usefulness of immunohistochemistry for mismatch repair protein and microsatellite instability examination in adenocarcinoma and background endometrium of sporadic endometrial cancer cases

Cited by 12 publications

References 27 publications

Prevalence of DNA Mismatch Repair Deficiency in Endometrial Cancer Using Immunohistochemistry

Prevalence of DNA Mismatch Repair Deficiency in Endometrial Cancer Using Immunohistochemistry

Microsatellite Instability: From the Implementation of the Detection to a Prognostic and Predictive Role in Cancers

Mismatch Repair Protein Expression Defects in Endometrioid Endometrial Adenocarcinoma

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