Analysis of 108 patients with endometrial carcinoma using the PROMISE classification and additional genetic analyses for MMR-D

Timmerman, S.; Rompuy, Anne‐Sophie Van; Gorp, Toon Van; Bempt, Isabelle Vanden; Brems, Hilde; Nieuwenhuysen, Els Van; Han, Sileny; Neven, P.; Victoor, Jasper; Laenen, Annouschka; Vergote, Ignace

doi:10.1016/j.ygyno.2020.01.019

Cited by 34 publications

(19 citation statements)

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“…21 studies were evaluated for eligibility after abstracts screening. Lastly, six studies were included in the systematic review and five studies in the meta-analysis [2,6,8,9,28,29]. Figure S1 graphically shows the study selection process.…”

Section: Study Selectionmentioning

confidence: 99%

Clinical features of ProMisE groups identify different phenotypes of patients with endometrial cancer

Raffone

Travaglino

Gabrielli

et al. 2021

Arch Gynecol Obstet

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Background The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) groups has identified four molecular prognostic groups of endometrial cancer (EC): POLE-mutated (POLE-mt), mismatch repair-deficient (MMR-d), p53-abnormal (p53-abn), p53-wild-type (p53-wt). These groups might have different pathogenesis and risk factors, and might occur in different phenotypes of patients. However, these data are still lacking. Objective To provide a clinical characterization of the ProMisE groups of EC. Methods A systematic review and meta-analysis was performed by searching seven electronic databases from their inception to December 2020, for all studies reporting clinical characteristics of EC patients in each ProMisE group. Pooled means of age and BMI and pooled prevalence of FIGO stage I and adjuvant treatment in each ProMisE group were calculated. Results Six studies with 1, 879 women were included in the systematic review. Pooled means (with standard error) and prevalence values were: in the MMR-d group, age = 66.5 ± 0.6; BMI = 30.6 ± 1.2; stage I = 72.6%; adjuvant treatment = 47.3%; in the POLE-mt group, age = 58.6 ± 2.7; BMI = 27.2 ± 0.9; stage I = 93.7%; adjuvant treatment = 53.6%; in the p53-wt group, age = 64.2 ± 1.9; BMI = 32.3 ± 1.4; stage I = 80.5%; adjuvant treatment = 45.3%; in the p53-abn group, age = 71.1 ± 0.5; BMI = 29.1 ± 0.5; stage I = 50.8%; adjuvant treatment = 64.4%. Conclusion The ProMisE groups identify different phenotypes of patients. The POLE-mt group included the youngest women, with the lower BMI and the highest prevalence of stage I. The p53-wt group included patients with the highest BMI. The p53-abn group included the oldest women, with the highest prevalence of adjuvant treatment and the lowest prevalence of stage I. The MMR-d group showed intermediate values among the ProMisE groups for all clinical features.

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Section: Study Selectionmentioning

confidence: 99%

Clinical features of ProMisE groups identify different phenotypes of patients with endometrial cancer

Raffone

Travaglino

Gabrielli

et al. 2021

Arch Gynecol Obstet

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“…For this reason, MMR/MSI status has been screened in a variety of tumors. Approximately 15% of colon tumors and 15–31% of uterine tumors are MSI-H ( 15 , 16 ). For hepatocellular carcinoma in non-alcoholic and non-virally infected livers, 16% of tumors (from 37 patients) were MSI-H ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

Mismatch Repair Deficiency and Microsatellite Instability in Triple-Negative Breast Cancer: A Retrospective Study of 440 Patients

et al. 2021

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PurposeTo investigate the status of mismatch repair (MMR) and microsatellite instability (MSI) in triple-negative breast cancer (TNBC) and to examine correlations between MMR/MSI status and clinicopathological parameters.MethodsWe retrospectively collected tissue samples from 440 patients with TNBC and constructed tissue microarrays. Protein expression of MLH1, MSH2, MSH6, and PMS2 was detected by immunohistochemistry (IHC). We also analyzed 195 patient samples using MSI polymerase chain reaction (PCR) testing. Correlations between MSI status and clinicopathological parameters and prognosis were analyzed.ResultsThe median age of the cohort was 49 years (range: 24–90 years) with a median follow-up period of 68 months (range: 1–170 months). All samples were positive for MLH1, MSH2, MSH6, and PMS2, except for one sample identified as MMR-deficient (dMMR) by IHC, with loss of MSH2 and intact MSH6 expression. MSI PCR revealed no case with high-frequency MSI (MSI-H), whereas 14 (7.2%) and 181 (92.8%) samples demonstrated low-frequency and absence of MSI events, respectively. The dMMR sample harbored low-frequency instability, as revealed by MSI PCR, and a possible EPCAM deletion in the tumor, as observed from next-generation sequencing. No correlations were detected between MMR or MSI status and clinicopathological parameters, programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) expression, or survival.ConclusionsThe incidence of dMMR/MSI-H is extremely low in TNBC, and rare discordant MSI PCR/MMR IHC results may be encountered. Moreover, MMR/MSI status may be of limited prognostic value. Further studies are warranted to explore other predictive immunotherapy biomarkers for TNBC.

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“…Patients with surgically staged IB diseases represent a heterogeneous population [23][24][25]. Landmark clinical trials have confirmed the beneficial necessity of EBRT in IB grade 3 patients but showed variability in IB grade 1/2 patients.…”

Section: Discussionmentioning

confidence: 99%

Real-World Evaluation of Modern Adjuvant Radiotherapy in Women with Stage IB Endometrial Cancer

Chen

Huang

et al. 2021

Cancers

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The optimal adjuvant treatment for stage IB endometrial cancer remains undefined. We investigated the benefit of modern adjuvant radiotherapy for women with stage IB endometrial cancer. We retrospectively reviewed patients with surgically staged, pure stage IB endometrioid adenocarcinoma (2010 to 2018). Adjuvant modern radiotherapy consists of external-beam radiotherapy (EBRT) by intensity, volumetric-modulated arc radiotherapy, or image-guided vaginal brachytherapy (VBT). The study included 180 stage IB patients. Patients with grade 3 diseases had frequent aggressive histology patterns (lymphovascular space invasion (LVSI); low uterine segment involvement) and experienced significantly shorter recurrence-free survival (RFS) and overall survival (OS) than patients with grade 1/2 diseases. Adjuvant modern radiotherapy decreased the incidence of acute/chronic grade ≥2 gastrointestinal toxicity. In IB grade 1/2 patients, EBRT significantly lengthened survival (RFS/OS); patients with age >60 years, myometrial invasion beyond the outer third, or LVSI benefited the most from EBRT. EBRT also significantly improved survival (RFS/OS) in IB grade 3 patients, where patients with bulky tumors or LVSI benefited the most from EBRT. Therefore, EBRT may be beneficial for all stage IB patients.

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Analysis of 108 patients with endometrial carcinoma using the PROMISE classification and additional genetic analyses for MMR-D

Cited by 34 publications

References 28 publications

Clinical features of ProMisE groups identify different phenotypes of patients with endometrial cancer

Clinical features of ProMisE groups identify different phenotypes of patients with endometrial cancer

Mismatch Repair Deficiency and Microsatellite Instability in Triple-Negative Breast Cancer: A Retrospective Study of 440 Patients

Real-World Evaluation of Modern Adjuvant Radiotherapy in Women with Stage IB Endometrial Cancer

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