Mismatch Repair Deficiency in Endometrial Cancer: Immunohistochemistry Staining and Clinical Implications

Doghri, Raoudha; Houcine, Yoldez; Boujelbène, Nadia; Driss, Maha; Charfi, Lamia; Abbès, Imen; Mrad, Karima; Sellami, R.

doi:10.1097/pai.0000000000000641

Cited by 17 publications

(25 citation statements)

References 23 publications

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“…In this study, we identi ed MMR-D TCs and investigated their mutation pro les, clinicopathological features, and prognostic signi cance. Previous studies have shown that the MMR-D phenotype occurs not only in hereditary non-polyposis CRC but also in endometrial cancer and breast cancer [21][22][23]. Mutations in MMR genes have been reported in approximately 14% of ATC cases [12].…”

Section: Discussionmentioning

confidence: 99%

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Correlation of Mismatch Repair Deficiency with Clinicopathological Features and Programmed Death-Ligand 1 Expression in Thyroid Carcinoma

Chen

Qiao

Tian

et al. 2022

Preprint

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Background Mutations in DNA mismatch repair (MMR) genes associated with thyroid carcinoma (TC) have rarely been reported, especially in East Asian populations. Methods We examined tumor tissue from a cohort of 241 patients diagnosed with TC between 2008 and 2020. MMR proteins were detected using tissue microarray-based immunohistochemistry in order to identify MMR-protein-deficient (MMR-D) and MMR-protein-intact (MMR-I) tumors. We retrospectively summarized the clinicopathologic characteristics of patients with MMR-D TC, measured the expression of PD-L1, and recorded overall survival (OS) and other clinical outcomes. Results In our cohort, there were 18 (7.5%) MMR-D (MLH1, MSH2, MSH6, and PMS2) patients, including 12 with papillary TC (PTC) (6.7%), 2 with poorly differentiated TC (PDTC) (4.7%), and 4 with anaplastic TC (ATC) (22.2%). Half of them (9/18) showed a specific deletion in MSH6, and 6 of them also carried variants in the MSH6 and PMS2 gene. Survival was significantly better in patients with MMR-D ATC than in those with MMR-I tumors (p=0.033). Four of the 18 MMR-D patients (22%) were found to be PD-L1 positive. Their OS was much shorter than that of PD-L1-negative patients. Conclusions MMR-D and PD-L1 positivity appear to be associated with clinicopathological characteristics and prognosis in TC. The results indicate that MMR status may have important prognostic significance in TC. Therefore, immune checkpoint inhibitors that target the PD-1/PD-L1 pathway may be a treatment option for TCs.

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Section: Discussionmentioning

confidence: 99%

“…It is worth noting that 1 of the included tumors was assessed for MSI-H/MMR-D and 2 were assessed for MSI-L/MMR-D status. Studies on SBA, endometrial cancer, and CRC have reported differences between MSI testing and IHC [21,22,25]. The other 11 cases showed microsatellite stability (MSS).…”

Section: Discussionmentioning

confidence: 99%

Correlation of Mismatch Repair Deficiency with Clinicopathological Features and Programmed Death-Ligand 1 Expression in Thyroid Carcinoma

Chen

Qiao

Tian

et al. 2022

Preprint

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“…The complete expression of all four MMR proteins was considered a case of pMMR. The loss of at least one MMR protein was considered a case of dMMR [ 34 ].…”

Section: Methodsmentioning

confidence: 99%

Using amide proton transfer-weighted MRI to non-invasively differentiate mismatch repair deficient and proficient tumors in endometrioid endometrial adenocarcinoma

Liu

Wang

et al. 2021

Insights Imaging

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Objectives To investigate the utility of three-dimensional (3D) amide proton transfer-weighted (APTw) imaging to differentiate mismatch repair deficient (dMMR) and mismatch repair proficient (pMMR) tumors in endometrioid endometrial adenocarcinoma (EEA). Methods Forty-nine patients with EEA underwent T1-weighted imaging, T2-weighted imaging, 3D APTw imaging, and diffusion-weighted imaging at 3 T MRI. Image quality and measurement confidence of APTw images were evaluated on a 5-point Likert scale. APTw and apparent diffusion coefficient (ADC) values were calculated and compared between the dMMR and pMMR groups and among the three EEA histologic grades based on the Federation of Gynecology and Obstetrics (FIGO) grading system criteria. Student’s t-test, analysis of variance with Scheffe post hoc test, and receiver operating characteristic analysis were performed. Statistical significance was set at p < 0.05. Results Thirty-five EEA patients (9 with dMMR tumors and 26 with pMMR tumors) with good image quality were enrolled in quantitative analysis. APTw values were significantly higher in the dMMR group than in the pMMR group (3.2 ± 0.3% and 2.8 ± 0.5%, respectively; p = 0.019). ADC values of the dMMR and pMMR groups were 0.874 ± 0.104 × 10−3 mm2/s and 0.903 ± 0.100 × 10−3 mm2/s, respectively. No significant between-group difference was noted (p = 0.476). No statistically significant differences were observed in APTw values or ADC values among the three histologic grades (p = 0.766 and p = 0.295, respectively). Conclusions APTw values may be used as potential imaging markers to differentiate dMMR from pMMR tumors in EEA.

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“…In endometrial cancer, the incidence of mutations in mismatch repair genes (MMR) is estimated at 17-30% [3][4][5]. The proteins of the MMR system are arranged in dimers, MLH1 together with PMS2 and MSH2 together with MSH6.…”

Section: Introductionmentioning

confidence: 99%

“…The study of the microsatellite instability (MSI) phenotype by these techniques is validated by standardized guidelines that confirm the direct association between MMR genetic study and protein assessment [7][8][9]. The distinction between patients with MSI phenotype and those with stable phenotype (MSS) allows the identification of patients who are candidates for MMR germline testing and the differentiation of Lynch syndrome cases from sporadic cases, as they present different anatomoclinical, prognostic and therapeutic factors [4].…”

Section: Introductionmentioning

confidence: 99%

An effective algorithm to detect the possibility of being MSI phenotype in endometrial cancer given the BMI status and histological subtype: a statistical study

Villa

González‐Dávila

Afonso³

et al. 2022

Clin Transl Oncol

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Purpose In endometrial cancer, the incidence of mutations in mismatch repair genes (MMR) is estimated at 17–30%. Patients with alterations at this level (MSI) are known to have different clinical and anatomopathological characteristics than those without this genetic alteration (MSS). In this study, we aim to identify the MSI phenotype in patients who underwent hysterectomy for endometrial cancer. We assessed the correlation of this phenotype with anatomoclinical parameters such as obesity and histological subtype. Methods/patients Clinical and anatomopathological data were collected from 147 patients diagnosed with endometrial cancer and an immunohistochemical study of MMR system proteins was performed. PMS2 and MSH6 proteins were evaluated as primary screening and subsequent evaluation of MLH1 and MSH6, respectively, if the former were negative. Statistical association between the anatomopathological data and the immunohistochemical result was analyzed. Results and conclusions 22.4% of our patients were MSI phenotype. We obtained statistically significant differences by multivariate analysis between endometrioid subtype and higher FIGO classification grade with MSI phenotype and obesity with MSS phenotype. Given these statistical results, we propose a function for predicting the probability of being MSI phenotype taking into account the histological subtype (endometrioid/non-endometrioid carcinoma) and FIGO grade as well as obesity. This prediction may be useful prior to hysterectomy, for genetic study of the MLH1 promoter and subsequent genetic counseling.

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Mismatch Repair Deficiency in Endometrial Cancer: Immunohistochemistry Staining and Clinical Implications

Cited by 17 publications

References 23 publications

Correlation of Mismatch Repair Deficiency with Clinicopathological Features and Programmed Death-Ligand 1 Expression in Thyroid Carcinoma

Correlation of Mismatch Repair Deficiency with Clinicopathological Features and Programmed Death-Ligand 1 Expression in Thyroid Carcinoma

Using amide proton transfer-weighted MRI to non-invasively differentiate mismatch repair deficient and proficient tumors in endometrioid endometrial adenocarcinoma

An effective algorithm to detect the possibility of being MSI phenotype in endometrial cancer given the BMI status and histological subtype: a statistical study

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