Loss of ARID1A Expression as a Favorable Prognostic Factor in Early-Stage Grade 3 Endometrioid Endometrial Carcinoma Patients

Kato, Mayumi Kobayashi; Yoshida, Hiroshi; Tanase, Yasuhito; Uno, Masaya; Ishikawa, Masatoshi; Kato, Tomoyasu

doi:10.3389/pore.2021.598550

Cited by 8 publications

(10 citation statements)

References 37 publications

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“…Owing to its low sensitivity, ARID1A does not appear adequate as a stand-alone diagnostic marker of premalignant EH, but it may be useful as a "rule-in" test for diagnosis of precancer, due to its excellent specificity. In agreement with our findings, ARID1A loss was reported to be associated with longer progression-free survival (P= 0.04) and that 7/9 of cases with recurrence in their study showed retained ARID1A expression (25) . Also, it was demonstrated that ARID1A mutations correlate with favorable survival in EEA using data from The Cancer Genome Atlas (44) .…”

Section: Combined Arid1a and Cd8+ Expression In Relation To Patient S...supporting

confidence: 92%

“…Also, it was demonstrated that ARID1A mutations correlate with favorable survival in EEA using data from The Cancer Genome Atlas (44) . A possible explanation for favorable prognosis of ARID1A loss in EEA is the relation of ARID1A loss with certain molecular subtypes of endometrial carcinoma those with MMR deficiency and POLE mutations that are considered a favorable prognostic factor in EEA (25) .…”

Section: Combined Arid1a and Cd8+ Expression In Relation To Patient S...mentioning

confidence: 99%

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The Diagnostic and Prognostic Significance of ARID1A and CD8+ Expression in Endometrial Hyperplasia and Endometrial Endometrioid Adenocarcinoma (Immunohistochemical study)

Sawi

Hassan²,

Youssef³

et al. 2022

Benha Medical Journal

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Background: Epigenetic driver mutations and tumor microenvironment could play an important and promising role in diagnosis, prognosis, and prediction of different endometrial lesions. Aim: To determine their putative diagnostic and prognostic value, this work analyzes the immunohistochemical (IHC) expression of ARID1A and CD8+ in endometrial hyperplasia (EH) and endometrioid endometrial adenocarcinoma (EEA). Material and methods: The 80 distinct endometrial lesions included in this retrospective study included (20) EH without atypia, (30) atypical EH (AEH), and (30) EEA. Clinicopathological characteristics and survival of examined cases were correlated with the IHC expression of ARID1A and CD8+. Results: ARID1A negative expression was significantly associated with EEA (46.7%) and AEH (30%), while its positivity was associated with EH without atypia cases (100%) (P<0.01). ARID1A showed 100% specificity and 38.3% sensitivity for premalignant (AEH) and malignant lesions. When compared to normal endometrium and EH without atypia, the amount of intraepithelial and stromal CD8+ expression revealed a significant difference between the examined cases (P<0.01 and P<0.05, respectively). ARID1A loss and high CD8+ expression was shown to be significantly correlated (P<0.01). Longer disease-free and recurrence-free survival were linked to ARID1A loss and high CD8+ expression. There was no discernible relationship between tumor grade, histologic type, lympho-vascular invasion, lymph node metastasis, or FIGO stage and either ARID1A or CD8+. Conclusion: ARID1A can be a reliable diagnostic indicator for premalignant lesions. ARID1A and CD8+ can each independently indicate a patient's increased chance of living longer and serve as biomarkers for the effectiveness of immunotherapy.

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Section: Combined Arid1a and Cd8+ Expression In Relation To Patient S...supporting

confidence: 92%

Section: Combined Arid1a and Cd8+ Expression In Relation To Patient S...mentioning

confidence: 99%

The Diagnostic and Prognostic Significance of ARID1A and CD8+ Expression in Endometrial Hyperplasia and Endometrial Endometrioid Adenocarcinoma (Immunohistochemical study)

Sawi

Hassan²,

Youssef³

et al. 2022

Benha Medical Journal

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Section: Methodsmentioning

confidence: 99%

“…All IHC tests, including those for p53 (DO7, prediluted, Dako, Glostrup, Denmark), ARID1A (rabbit polyclonal, 1:2000, Sigma), PMS2 (EP51, prediluted, Dako), and MSH6 (EP49, prediluted, Dako), were performed as described in our previous study. 21 , 22 Furthermore, an IHC test for CTNNB1, the primary antibody of β‐catenin (clone14, 1:500; BD Bioscience), was performed in this study. The term “aberrant p53 staining pattern” refers to either a strong and diffuse nuclear staining pattern (>80% of carcinoma cells) or completely negative (“null pattern”) staining pattern of carcinoma cells, with staining of the adjacent nontumor cells serving as an internal positive control.…”

Section: Methodsmentioning

confidence: 99%

Clinical impact of genetic alterations of CTNNB1 in patients with grade 3 endometrial endometrioid carcinoma

Kato

Asami

Takayanagi³

et al. 2022

Cancer Science

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To identify prognostic factors in patients with grade 3 (high‐grade) endometrial endometrioid carcinoma, we evaluated the spectrum of genomic alterations and examined whether previously reported molecular subtypes of endometrial carcinoma were adapted to clinical outcome prediction. Seventy‐five Japanese patients with grade 3 endometrial endometrioid carcinoma, who underwent a potentially curative resection procedure between 1997 and 2018 at the National Cancer Center Hospital, were included. We classified the patients into four risk groups of the disease based on the Proactive Molecular Risk Classifier for Endometrial Cancer. Genomic alterations in PTEN, ARID1A, TP53, and PIK3CA were detected in more than 30% of the patients. Overall survival and recurrence‐free survival of patients with genomic alterations in CTNNB1 were poorer than those of patients with wild‐type CTNNB1 (p = 0.006 and p = 0.004, respectively). Compared with that of alterations prevalent in Caucasians, the frequency of genomic alterations in POLE and TP53 was higher in our study than in The Cancer Genome Atlas dataset (p = 0.01 and p = 0.01, respectively). The tendency for recurrence‐free survival in the POLE exonuclease domain mutation group was better than that in the TP53 mutation and mismatch repair‐deficient groups (p = 0.08 and p = 0.07, respectively), consistent with the Proactive Molecular Risk Classifier for Endometrial Cancer risk classifier definition. The CTNNB1 mutation is a potential novel biomarker for the prognosis of patients with grade 3 endometrial endometrioid carcinoma, and prognosis classification using Proactive Molecular Risk Classifier for Endometrial Cancer may help screen Japanese patients with the disease.

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“…Among those, NSMP is the most heterogeneous group and the one for which novel biomarkers of risk stratification are urgently needed. To this aim, in the present study we have applied the aforementioned molecular classification to a cohort of high-risk ECs and further investigated the expression of additional markers with known prognostic potential in EC—estrogen (ER) and progesterone (PR) receptors [ 11 , 12 ], L1 Cell Adhesion Molecule (L1CAM) [ 12 , 13 , 14 , 15 ], Catenin Beta 1 (CTNNB1) [ 16 ], AT-Rich Interaction Domain 1A (ARID1A) [ 17 , 18 ], ki-67 proliferation index [ 19 ], and intratumoral immune cell infiltrate [ 20 ]—within the four molecular subgroups. Specifically, we analyzed the potential of those additional markers to further stratify the NSMP category, characterized by marked heterogeneous clinicopathologic features and prognosis.…”

Section: Introductionmentioning

confidence: 99%

Integrated Biomarker Analysis Reveals L1CAM as a Potential Stratification Marker for No Specific Molecular Profile High-Risk Endometrial Carcinoma

Ravaggi

Capoferri²,

Ardighieri³

et al. 2022

Cancers

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Histopathologic assessment of high-risk endometrial cancer (EC) suffers from intersubject variability and poor reproducibility. The pragmatic classification in four molecular subgroups helps to overcome these limits, showing a significant prognostic value. The “no specific molecular profile” (NSMP) is the most heterogeneous EC subgroup, requiring further characterization to better guide its clinical management. DNA sequencing of POLE exonuclease domain and immunohistochemistry for PMS2, MSH6, and p53 were performed in order to stratify a cohort of 94 high-risk EC patients in the four molecular subgroups. Moreover, a panel of seven additional biomarkers was tested. Patients were found to be 16% POLE-mutated, 36% mismatch repair-deficient, 27% p53-abnormal, and 21% NSMP. In the multivariable model, molecular groups confirmed their significant association with disease-specific survival and progression-free survival, with p53-abnormal and NSMP endometrial cancer characterized by poor outcomes. Among the additional evaluated biomarkers, L1CAM was the only one with a significant prognostic value within the NSMP subgroup. NSMP/L1CAM-positive patients experienced the worst outcome and were “early-relapsing” after platinum-based chemotherapy, with a significantly shorter platinum-free interval compared to L1CAM-negative patients. L1CAM appears to be a promising candidate as a prognostic and predictive biomarker in the high-risk NSMP subgroup, which is actually known to lack specific molecular markers.

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Loss of ARID1A Expression as a Favorable Prognostic Factor in Early-Stage Grade 3 Endometrioid Endometrial Carcinoma Patients

Cited by 8 publications

References 37 publications

The Diagnostic and Prognostic Significance of ARID1A and CD8+ Expression in Endometrial Hyperplasia and Endometrial Endometrioid Adenocarcinoma (Immunohistochemical study)

The Diagnostic and Prognostic Significance of ARID1A and CD8+ Expression in Endometrial Hyperplasia and Endometrial Endometrioid Adenocarcinoma (Immunohistochemical study)

Clinical impact of genetic alterations of CTNNB1 in patients with grade 3 endometrial endometrioid carcinoma

Integrated Biomarker Analysis Reveals L1CAM as a Potential Stratification Marker for No Specific Molecular Profile High-Risk Endometrial Carcinoma

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