News - POLE mutation - LARVOL VERI

Endometrial adenocarcinoma with mutations in POLE, TP53 genes and microsatellite instability (PubMed, Arkh Patol)

At the same time POLE-mutated endometrial carcinomas recur rarely and exhibit the excellent prognosis. Here we report the rare case of 65 y.o. female patient with endometrioid carcinoma sharing immunohistochemical and molecular features of TP53-aberrant, MMR deficient and POLE-mutated subtypes.

3 days ago

Journal • Microsatellite instability

TP53 (Tumor protein P53) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)

TP53 mutation • MSI-H/dMMR • POLE mutation

Next-generation sequencing in the molecular classification of endometrial carcinomas: Experience with 270 cases suggesting a potentially more aggressive clinical behavior of multiple classifier endometrial carcinomas. (PubMed, Virchows Arch)

Our findings suggest that combining immunohistochemistry with NGS offers a more reliable classification of ECs, including 'multiple classifier' cases, which, based on our observations, tend to exhibit aggressive behavior. Additionally, our data highlight the complex genetic background of NSMP ECs, which can facilitate further stratification of tumors within this group and potentially help select patients for dedicated clinical trials.

5 days ago

Journal • Next-generation sequencing

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon)

TP53 mutation • PIK3CA mutation • PTEN mutation • POLE mutation

PD-L1 Expression and Immune Infiltration Across Molecular Subtypes of Endometrial Cancer: An Integrative-Analysis of Molecular Classification and Immune Subtypes. (PubMed, Hum Pathol)

Higher CD8+ T cell density was a prognostic marker for disease-free survival in EC, including within NSMP (p<0.05). In summary, the four WHO molecular subtypes of EC exhibit distinct TIME subtypes, complementing molecular classification and providing insights for optimizing EC immunotherapy strategies.

9 days ago

Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • CD20 (Membrane Spanning 4-Domains A1) • POLE (DNA Polymerase Epsilon) • CD8 (cluster of differentiation 8) • CD68 (CD68 Molecule)

PD-L1 expression • TP53 mutation • MSI-H/dMMR • POLE mutation • CD8-H

VENTANA PD-L1 (SP263) Assay

12d

Clinicopathological and molecular genetic features of POLE-mutated endometrioid carcinoma (PubMed, Zhonghua Bing Li Xue Za Zhi)

Correct interpretation of molecular results, accurate identification and classification are important for predicting prognosis and avoiding overtreatment. However, a small number of cases may have recurrence and metastasis, and therefore it is necessary to make a reasonable treatment plan based on the comprehensive judgment of other high risk factors.

12 days ago

Retrospective data • Journal • MSi-H Biomarker

TP53 (Tumor protein P53) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)

TP53 mutation • MSI-H/dMMR • POLE mutation

20d

POLE-mutated uterine carcinosarcomas: a clinicopathologic and molecular study of 11 cases. (PubMed, Mod Pathol)

Our study supports full molecular classification of UCS. We also raise awareness for potentially assessing POLE mutation allele fraction and clonality in the consideration of classifying a tumor as POLEmut.

20 days ago

Journal

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon) • FBXW7 (F-Box And WD Repeat Domain Containing 7)

TP53 mutation • PIK3CA mutation • PTEN mutation • ARID1A mutation • POLE mutation • TP53 expression

22d

The advent of immune checkpoint inhibition for the treatment of patients with primary advanced or recurrent dMMR/MSI high endometrial cancer in 2025. (PubMed, Curr Opin Obstet Gynecol)

Immunotherapy therapy has revolutionized the treatment of endometrial cancer in both upfront and recurrent settings, with molecular subtyping identifying patients most likely to benefit, especially those with dMMR/MSI-H tumors.

22 days ago

Journal • Checkpoint inhibition • MSi-H Biomarker • IO biomarker • Metastases

MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)

MSI-H/dMMR • POLE mutation

29d

Functions, interactions and prognostic role of POLE: a bioinformatics analysis. (PubMed, J Gynecol Oncol)

Mutations in POLE might affect DNA polymerase epsilon function. These mutations also affect interactions with other proteins like proteins involved in different DNA repairing mechanisms. POLE mutations may lead to platinum resistance, but they can also trigger an immune response that improves prognosis.

29 days ago

Journal

POLE (DNA Polymerase Epsilon) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)

POLE mutation • POLE V411L

Prognostic and therapeutic implication of molecular classification including L1CAM expression in high-risk endometrial cancer. (PubMed, Gynecol Oncol)

L1CAM is an additional adverse factor in the p53 abnormal and NSMP groups. These groups need special attention in studies intensifying adjuvant treatment.

1 month ago

Journal

POLE (DNA Polymerase Epsilon) • L1CAM (L1 cell adhesion molecule)

TP53 mutation • POLE mutation

Molecular classification and adjuvant treatment in endometrioid endometrial cancer with microcystic elongated and fragmented (MELF) invasion pattern. (PubMed, BMC Womens Health)

The presence of the MELF pattern in EEC should be incorporated into decision-making regarding adjuvant therapy. The use of adjuvant treatment should be tailored based on histology and molecular type.

1 month ago

Retrospective data • Journal

TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon)

TP53 mutation • MSI-H/dMMR • POLE mutation

Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations (AIOM 2024)

4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.

1 month ago

Clinical • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • POLE (DNA Polymerase Epsilon) • MDM2 (E3 ubiquitin protein ligase) • PTCH1 (Patched 1) • NF2 (Neurofibromin 2) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • BRCA2 mutation • BRCA1 mutation • TMB-H • PIK3CA mutation • MET amplification • ALK rearrangement • FGFR1 amplification • POLE mutation • NF1 mutation • MDM2 amplification • RET mutation • PTCH1 mutation • NF2 mutation • ROS1 mutation • BRCA mutation • ALK rearrangement + PIK3CA mutation • PTCH1 rearrangement • NTRK fusion

FoundationOne® CDx

Opdivo (nivolumab) • Yervoy (ipilimumab) • Alecensa (alectinib) • Erivedge (vismodegib)

PIK3CA mutations in endometrial cancer: a pre-planned biomarker analysis from the phase II MITO END-3 study of carboplatin and paclitaxel with or without avelumab in advanced or recurrent endometrial cancer (AIOM 2024)

The frequent alterations of the PI3K pathway in gynecological cancers could emerge as new treatment target. Our data confirm the high frequency of PIK3CA mutations establishing EC as an ideal candidate for testing of PI3K inhibitors regardless of the TCGA classification. Moreover, these data confirm that other targetable mutations are present also in MSS EC group thus suggesting that new target agents should be explored.

1 month ago

P2 data • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Metastases

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon)

TP53 mutation • MSI-H/dMMR • PIK3CA mutation • TP53 wild-type • PIK3CA H1047R • PTEN mutation • ARID1A mutation • POLE mutation • PIK3CA E545K • PIK3CA E545 • PIK3CA E542 • PIK3CA H1047L • PIK3CA mutation + PTEN mutation • PIK3CA C420R • PIK3CA E545A • PIK3CA E545G • PIK3CA Q546 • PIK3CA Q546R

FoundationOne® CDx

carboplatin • paclitaxel • Bavencio (avelumab)

Advantages of next-generation sequencing (NGS) in the molecular classifi cation of endometrial carcinomas - our experience with 270 cases. (PubMed, Ceska Gynekol)

In comparison with recommended diagnostic algorithms, NGS provides a more reliable classification of EC into particular molecular subgroups. Furthermore, NGS reveals the complex molecular genetic background in individual ECs, which is especially significant within ECs with no specific molecular profile. These data can serve as a springboard for the research of therapeutic programs committed to targeted therapy in this type of tumor.

1 month ago

Journal • Next-generation sequencing • BRCA Biomarker

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PMS2 (PMS1 protein homolog 2) • BCOR (BCL6 Corepressor) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • POLD1 (DNA Polymerase Delta 1)

TP53 mutation • PIK3CA mutation • PTEN mutation • POLE mutation

Radiation and TSR-042 (Dostarlimab) in People With Endometrial Cancer After They Receive Surgery (clinicaltrials.gov)

P2, N=62, Recruiting, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Recruiting | N=31 --> 62 | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2025 --> Feb 2026

1 month ago

Enrollment open • Enrollment change • Trial completion date • Trial primary completion date • Checkpoint inhibition • Mismatch repair • Surgery • Checkpoint block • Metastases

MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)

MSI-H/dMMR • POLE mutation

Jemperli (dostarlimab-gxly)

2ms

Durvalumab for MSI-H or POLE Mutated Metastatic Colorectal Cancer (clinicaltrials.gov)

P2, N=33, Completed, Asan Medical Center | Active, not recruiting --> Completed

2 months ago

Trial completion • Mismatch repair • Tumor mutational burden • Metastases

POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)

MSI-H/dMMR • POLE mutation

Imfinzi (durvalumab) • oxaliplatin • irinotecan

3ms

Effect of hemoglobin, albumin, lymphocyte, and platelet score on prognosis in intermediate-risk endometrial cancer according to molecular-based classification. (PubMed, J Obstet Gynaecol Res)

MMR deficiency and NSMP have been considered intermediate-risk groups for endometrial cancer and are a heterogeneous group. Although the use of the HALP score to reduce this heterogeneity is successful in predicting OS, it is not sufficient for PFS.

3 months ago

Journal

TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon)

TP53 mutation • POLE mutation

3ms

A Phase 1 Trial of Trebananib, an Angiopoietin 1 and 2 Neutralizing Peptibody, Combined with Pembrolizumab in Patients with Advanced Ovarian and Colorectal Cancer. (PubMed, Cancer Immunol Res)

After development of acquired resistance, biopsy of one patient's KRAS wild-type, ERBB2 amplified tumor showed a substantial decline in tumor-associated T cells and an increase in immunosuppressive intratumoral macrophages. Future studies are needed to carefully assess whether clinicogenomic features, such as lack of liver metastases, ERBB2 amplification, and left-sided tumors, can predict increased sensitivity to PD1 immunotherapy combinations.

3 months ago

P1 data • Journal • PD(L)-1 Biomarker • IO biomarker • Metastases

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • POLE (DNA Polymerase Epsilon)

HER-2 amplification • POLE mutation • KRAS wild-type • RAS wild-type

Keytruda (pembrolizumab) • trebananib (AMG 386)

3ms

Predictors of Node Positivity in Endometrial Cancer (clinicaltrials.gov)

P=N/A, N=200, Recruiting, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano | Not yet recruiting --> Recruiting | N=100 --> 200 | Trial completion date: Dec 2023 --> Jan 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

3 months ago

Enrollment open • Enrollment change • Trial completion date • Trial primary completion date

TP53 (Tumor protein P53) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)

TP53 mutation • MSI-H/dMMR • POLE mutation

3ms

Clinical implications of next generation sequencing for the classification of endometrial carcinoma (ECP 2024)

Molecular characterization of endometrial carcinoma into subgroups has important implications for prognosis and treatment. Next-generation sequencing is a powerful tool that provides reliable results consistent with surrogate immunohistochemical markers. By performing a molecular profile of patients, NGS can identify important genetic mutations such as p53, POLE and MSI, as well as variants like CTNNB1 that have prognostic value.

3 months ago

Clinical • Next-generation sequencing

TP53 (Tumor protein P53) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)

TP53 mutation • POLE mutation • TP53 expression

OncoKitDx

3ms

High tumour mutation burden assessed by comprehensive molecular genetic profiling as a targeted therapeutic option for solid tumours (ECP 2024)

Eight patients received immune checkpoint inhibitor therapy (7 pembrolizumab and 1 atezolizumab). TMB status determined by CGP was found to be an effective method for predicting the response to immune checkpoint inhibitors; both PFS and OS improved markedly for patients who received therapy. In our experience, TMB status, along with microsatellite instability and POLE mutation status, can be used as a predictive biomarker for therapeutic response in a wide range of histologies.

3 months ago

Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker

TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)

TMB-H • POLE mutation

Oncomine™ Comprehensive Assay Plus

Keytruda (pembrolizumab) • Tecentriq (atezolizumab)

3ms

Deciphering the immune landscape of gastro-entero-pancreatic high-grade neuroendocrine neoplasms could help in tailoring medical treatment? (ECP 2024)

Immunotherapy has shown poor efficacy in the unselected population of HG-GEP-NENs because the immune microenvironment landscape was scant in HG-GEP-NENs at transcriptomic analysis and PD-L1 expression was absent. Thus, there is a great need to identify subsets of HG-GEP-NENs responsive to immunotherapy approaches. The present results addressed GEP-NECs with high proliferation index as sensible candidates to immunotherapy due to the enrichment in TMB-high and MSI coupled with higher CD4+ and CD8+ T cell expression.

3 months ago

Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • CD8 (cluster of differentiation 8) • MSH2 (MutS Homolog 2) • CD4 (CD4 Molecule)

PD-L1 expression • TMB-H • PD-L1 negative • POLE mutation

TruSight Oncology 500 Assay

3ms

Concurrent POLE hotspot mutations and mismatch repair deficiency/microsatellite instability in endometrial cancer: A challenge in molecular classification. (PubMed, Gynecol Oncol)

POLEmut/MMRd ECs may be genetically distinct. Further studies are needed to assess the impact on outcomes and treatment response within this population.

3 months ago

Journal • Mismatch repair • Tumor mutational burden • Microsatellite instability • MSi-H Biomarker

TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)

TMB-H • MSI-H/dMMR • POLE mutation

4ms

The game-changing impact of POLE mutations in oncology-a review from a gynecologic oncology perspective. (PubMed, Front Oncol)

Therapeutic modalities for these hypermutated tumors are also an important consideration, including the need for or de-escalation of adjuvant treatments and the response to immune therapy. This review addresses the critical role of POLE mutations in gynecologic oncology and oncology in general, focusing on definitions, variants, underlying pathogenic mechanisms, upcoming developments in the field, and the clinic behavior associated with such mutations.

4 months ago

Review • Journal • Tumor mutational burden

TMB (Tumor Mutational Burden) • POLE (DNA Polymerase Epsilon)

TMB-H • POLE mutation • POLE EDM

4ms

Endometrial carcinomas with ambiguous histology often harbor TP53 mutations. (PubMed, Virchows Arch)

In conclusion, based on this series, the molecular landscape of endometrial carcinomas with ambiguous histology is dominated by TP53 mutations and the absence of POLE mutations, with heterogeneous molecular profile with respect to other genes. A high proportion of these tumors is clinically aggressive.

4 months ago

Journal • BRCA Biomarker

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • MUC16 (Mucin 16, Cell Surface Associated) • FAT1 (FAT atypical cadherin 1) • JAK1 (Janus Kinase 1) • FAT4 (FAT Atypical Cadherin 4) • CSMD3 (CUB And Sushi Multiple Domains 3) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)

TP53 mutation • PIK3CA mutation • POLE mutation

7ms

A comprehensive analysis of POLE/POLD1 genomic alterations in colorectal cancer. (PubMed, Oncologist)

Patients with POLE/POLD1 mutations exhibited significant differences across immunological markers (ie, TMB, MMR, and MSI-H) and molecular co-alterations. Those with short variant mutations represented 18% of the POLE/POLD1 cohort and 0.4% of the total cohort examined. This group of patients had a median TMB of 159 mut/Mb (range 34-488), representing the ultra-hypermutated phenotype. This group of patients is important to identify given the potential for exceptional response to immune checkpoint inhibitors.

7 months ago

Journal • Tumor mutational burden • MSi-H Biomarker • BRCA Biomarker • IO biomarker

ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)

TMB-H • MSI-H/dMMR • ATM mutation • POLE mutation • ALK mutation • RET mutation • POLD1 mutation • POLE mutation + POLD1 mutation

Tempus xT Assay

7ms

Value of Molecular Typing Combined with Integrated Positron Emission Tomography/Magnetic Resonance Imaging in Risk Stratification of Endometrial Cancer. (PubMed, Int J Womens Health)

Molecular typing combined with the integrated PET/MRI semi-quantitative SUV max index can predict the low/medium risk group of endometrial cancer and the medium-high/high risk group, and the cut-off value of SUV max for predicting the risk of early endometrial cancer was 14.72 (sensitivity 66.7%, specificity 68.7%). Molecular typing combined with integrated PET/MRI semi-quantitative indicators is useful to achieve risk stratification in patients diagnosed with endometrial cancer and guide individualized treatment.

7 months ago

Journal • MRI

TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon)

POLE mutation

7ms

Enrichment for the POLE mutated against p53 wild subtype using clinicopathologic factors and cyclin B1 immunohistochemistry in endometrial cancer. (PubMed, J Gynecol Oncol)

No abstract available

7 months ago

Journal

TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon) • CCNB1 (Cyclin B1)

TP53 mutation • POLE mutation

8ms

MITO END-3: Efficacy of Avelumab immunotherapy according to molecular profiling in first-line endometrial cancer therapy. (PubMed, Ann Oncol)

The MITO END-3 trial results suggest that TP53 mutation is associated with a poor effect of avelumab, while mutations of PTEN and ARID1A are related to a positive effect of the drug in patients with advanced endometrial cancer.

8 months ago

Journal • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon)

TP53 mutation • BRCA2 mutation • BRCA1 mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • TP53 wild-type • PTEN mutation • ARID1A mutation • POLE mutation

carboplatin • paclitaxel • Bavencio (avelumab)

8ms

Prognostic value of molecular classification in stage IV endometrial cancer. (PubMed, Int J Gynecol Cancer)

The distribution of the molecular subclasses in stage IV endometrial cancer patients differed substantially from the distribution in stage I-III endometrial cancer patients, with the unfavorable subclasses being more frequently present. Although the molecular classification was not prognostic in stage IV endometrial cancer, it could guide adjuvant treatment decisions.

8 months ago

Journal • Metastases

ER (Estrogen receptor) • POLE (DNA Polymerase Epsilon)

ER positive • MSI-H/dMMR • POLE mutation • ER negative

8ms

Predicting the Risk of nOdal disease with histological and Molecular features in Endometrial cancer: the prospective PROME trial. (PubMed, Int J Gynecol Cancer)

Our data suggest that molecular classification does not seem useful to tailor the need of nodal dissection in apparent early-stage endometrial cancer. p53 abnormality predicts the risk of having advanced disease at presentation. Further external validation is needed.

8 months ago

Journal • MSi-H Biomarker

TP53 (Tumor protein P53) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)

TP53 mutation • MSI-H/dMMR • POLE mutation

9ms

Pembrolizumab in Ultramutated and Hypermutated Endometrial Cancer (clinicaltrials.gov)

P2, N=25, Active, not recruiting, Yale University | Trial completion date: Jun 2024 --> Oct 2025 | Trial primary completion date: Jun 2024 --> Oct 2025

9 months ago

Trial completion date • Trial primary completion date • IO biomarker

MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)

POLE mutation • POLD1 mutation • POLE mutation + POLD1 mutation

Keytruda (pembrolizumab)

9ms

Molecular profile in endometrial carcinoma: can we predict the lymph node status? A systematic review and meta-analysis. (PubMed, Clin Transl Oncol)

The presence of LNM seems to be influenced by molecular classification. P53-abnormal group presents the highest rate of nodal involvement, and POLE-mutated the lowest.

9 months ago

Retrospective data • Review • Journal

POLE (DNA Polymerase Epsilon)

POLE mutation

9ms

High prevalence of "non-pathogenic" POLE mutation with poor prognosis in a cohort of endometrial cancer from South India. (PubMed, Int J Gynaecol Obstet)

This study identified a unique set of POLE mutations in Indian EC patients associated with poor prognosis, which were particularly pronounced in advanced stages. Advanced stage of presentation, type of POLE mutations, and possibly ethnicity are predictors of adverse outcomes in POLE-mutated EC. The present study highlights ethnicity as a determinant of phenotypic expression of genetic change.

9 months ago

Journal

POLE (DNA Polymerase Epsilon)

POLE mutation

9ms

Morules and β-catenin predict POLE mutation status in endometrial cancer: A pathway to more cost-effective diagnostic procedures. (PubMed, Am J Clin Pathol)

Our findings suggest that the presence of either morules or nuclear β-catenin expression in EEC could practically rule out the presence of POLE mutations. These morphologic and immunohistochemical features can be used as preliminary screening tools for POLE mutations, offering significant savings in time and resources and potentially enhancing clinical decision-making and patient management strategies. However, further validation in larger, multi-institutional studies is required to fully understand the implications of these findings on clinical practice.

9 months ago

Journal • HEOR • Cost-effectiveness • Cost effectiveness

POLE (DNA Polymerase Epsilon) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)

POLE mutation

9ms

Pembrolizumab in Ultramutated and Hypermutated Endometrial Cancer (clinicaltrials.gov)

P2, N=25, Active, not recruiting, Yale University | Trial completion date: Dec 2028 --> Jun 2024 | Trial primary completion date: Dec 2023 --> Jun 2024

9 months ago

Trial completion date • Trial primary completion date • IO biomarker

MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)

POLE mutation • POLD1 mutation • POLE mutation + POLD1 mutation

Keytruda (pembrolizumab)

9ms

Assessing the New 2020 ESGO/ESTRO/ESP Endometrial Cancer Risk Molecular Categorization System for Predicting Survival and Recurrence. (PubMed, Cancers (Basel))

The 2020 ESGO molecular classification system demonstrated practical utility and significantly influenced survival outcomes. Immunohistochemistry for TP53 and MMR, along with POLE sequencing, facilitated substantial patient reclassification, underscoring the clinical relevance of molecular risk categories in EC management.

9 months ago

Journal

TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon)

TP53 mutation • MSI-H/dMMR • POLE mutation

9ms

The Clinical and Pathological Characteristics of POLE-Mutated Endometrial Cancer: A Comprehensive Review. (PubMed, Cancer Manag Res)

This subtype exhibits a high tumor mutation burden, abundant lymphocyte infiltration, and a favorable prognosis, making it a promising candidate for immune checkpoint inhibitor therapy. This paper presents a comprehensive review of the clinical and pathological characteristics, outcomes, treatment advancements, pathogenic POLE gene detection, and alternative testing methods for POLE-mutated endometrial cancer.

9 months ago

Review • Journal • Tumor mutational burden • IO biomarker

TMB (Tumor Mutational Burden) • POLE (DNA Polymerase Epsilon)

TMB-H • POLE mutation

10ms

AcSé: Secured Access to Nivolumab for Adult Patients With Selected Rare Cancer Types (clinicaltrials.gov)

P2, N=269, Completed, UNICANCER | Active, not recruiting --> Completed

10 months ago

Trial completion

MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)

POLE mutation

Opdivo (nivolumab)

10ms

Potential of molecular classification to guide fertility-sparing management among young patients with endometrial cancer. (PubMed, Gynecol Oncol)

Lastly, the no specific molecular profile (or p53 wild-type) tumors, while having a relatively good prognosis, are heterogeneous and require more precise biomarkers to effectively guide therapy for those with poorer prognoses. Addressing these research gaps will lead to more precise guidelines to ensure optimal selection for fertility-sparing treatment.

10 months ago

Journal

TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon)

TP53 mutation • MSI-H/dMMR • TP53 wild-type • POLE mutation • TP53 expression • POLE EDM

10ms

Tumor mutational burden assessment and standardized bioinformatics approach using custom NGS panels in clinical routine. (PubMed, BMC Biol)

We herein propose a TMB calculation method and a bioinformatics tool that is customizable to different NGS panels and sample types. We were not able to retrieve TMB values from FO algorithm using our own algorithm and NGS panel.

10 months ago

Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Next-generation sequencing

TMB (Tumor Mutational Burden) • POLE (DNA Polymerase Epsilon)

TMB-H • POLE mutation

FoundationOne® CDx

Keytruda (pembrolizumab)

10ms

Multiple duodenal epithelial tumors in a patient with polymerase proofreading-associated polyposis in POLE variant. (PubMed, Clin J Gastroenterol)

In addition, duodenal tumors frequently coexist in patients with PPAP-carrying POLE variants, while the endoscopic treatment for duodenal tumors becomes safe and useful with several new approaches. Therefore, surveillance EGD is necessary in such patients for the early detection and treatment of duodenal tumors.

10 months ago

Journal

POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)

POLE mutation

10ms

Nivolumab Ipilimumab in Patients With hyperMutated Cancers Detected in Blood (NIMBLe) (clinicaltrials.gov)

P2, N=4, Terminated, Canadian Cancer Trials Group | Active, not recruiting --> Terminated; cfDNA screening data found that the prevalence of POLE/POLD1 mutations was lower than expected. It was determined that there are no feasible options to amend this study in a fashion that would not be duplicative of other currently accruing trials.

10 months ago

Trial termination

POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)

POLE mutation • POLD1 mutation • POLE mutation + POLD1 mutation

Opdivo (nivolumab) • Yervoy (ipilimumab)

10ms

Molecular profile is a strong predictor of the pattern of recurrence in patients with endometrial cancer. (PubMed, Int J Gynecol Cancer)

Endometrial cancer featured different patterns of recurrence depending on the molecular profile. p53-abnormal molecular profiling was the only independent risk factor for peritoneal relapse, while non-specific molecular profile showed a strong association with distant failures.

10 months ago

Journal

POLE (DNA Polymerase Epsilon)

TP53 mutation • MSI-H/dMMR • POLE mutation