Clinicopathologic vs. Molecular Integrated Prognostication of Endometrial Carcinoma by European Guidelines

Loukovaara, Mikko; Pasanen, Annukka; Bützow, Ralf

doi:10.3390/cancers14030651

Cited by 12 publications

(9 citation statements)

References 18 publications

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“…To the best of our knowledge, this large series represents one of the first applications of the new molecular classification in clinical practice. Consistent with our results, a recent Finnish study using the ProMisE schema for molecular classification observed a risk group migration in 6.0% of patients, who were downshifted or upshifted to another risk group due to a pathogenic POLE mutation or abnormal p53 staining, respectively 26. Similarly, in an earlier study from the Karolinska Institute the molecular classification according to the ESGO/ESTRO/ESP guidelines determined a 7% change in risk group as compared with the 2016 ESMO/ESGO/ESTRO classification system based only on clinicopathologic characteristics 27.…”

Section: Discussionsupporting

confidence: 92%

A novel algorithm to implement the molecular classification according to the new ESGO/ESTRO/ESP 2020 guidelines for endometrial cancer

Betella

Fumagalli

Raviele

et al. 2022

Int J Gynecol Cancer

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ObjectiveTo compare the risk class attribution with molecular classification unknown to those with molecular classification known, according to the European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) 2020 guidelines on endometrial cancer, with a focus on risk group migration. Additionally, to evaluate the capability of a novel molecular analysis algorithm to reduce the number of required tests.MethodsWe conducted a retrospective study including all consecutive patients with endometrial cancer undergoing surgery and comprehensive molecular analyses between April 2019 and December 2021. Molecular analyses including immunohistochemistry for p53 and mismatch repair (MMR) proteins, and DNA sequencing for POLE exonuclease domain were performed to classify tumors as POLE-mutated (POLE), MMR-deficient (MMR-d), p53 abnormal (p53abn), or non-specific molecular profile (NSMP). The two risk classifications of the ESGO/ESTRO/ESP 2020 guidelines were compared to estimate the proportion of patients in which the molecular analysis was able to change the risk class attribution. We developed a novel algorithm where the molecular analyses are reserved only for patients in whom incorporation of the molecular classification could change the risk class attribution.ResultsA total of 278 patients were included. Molecular analyses were successful for all cases, identifying the four subgroups: 27 (9.7%) POLE, 77 (27.7%) MMR-d, 49 (17.6%) p53abn, and 125 (45.0%) NSMP. Comparison of risk class attribution between the two classification systems demonstrated discordance in the risk class assignment in 19 (6.8%, 95% CI 4.2% to 10.5%) cases. The application of our novel algorithm would have led to a reduction in the number of POLE sequencing tests by 67% (95% CI 61% to 73%) and a decrease of p53 immunohistochemistry by 27% (95% CI 22% to 33%), as compared with the application of molecular classification to all patients.ConclusionMolecular categorization of endometrial cancer allows the reallocation of a considerable proportion of patients in a different risk class. Furthermore, the application of our algorithm enables a reduction in the number of required tests without affecting the risk classification.

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Section: Discussionsupporting

confidence: 92%

A novel algorithm to implement the molecular classification according to the new ESGO/ESTRO/ESP 2020 guidelines for endometrial cancer

Betella

Fumagalli

Raviele

et al. 2022

Int J Gynecol Cancer

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“…To the best of our knowledge, our study represents one of the first validations of the ESGO/ESTRO/ESP guidelines in the clinical setting. In agreement with our results, some studies have shown risk group migration in about 6–7% of patients compared with the classification system based on clinicopathologic features alone ( 29 – 31 ). Consistent with our findings, the presence of pathogenic POLE mutation or abnormal p53 staining results in a shift to a lower or higher risk class, respectively.…”

Section: Discussionsupporting

confidence: 93%

Integrated clinicopathologic and molecular analysis of endometrial carcinoma: Prognostic impact of the new ESGO-ESTRO-ESP endometrial cancer risk classification and proposal of histopathologic algorithm for its implementation in clinical practice

Biase

Maloberti²,

Corradini³

et al. 2023

Front. Med.

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IntroductionThe European Society of Gynecologic Oncology/European Society of Radiation Therapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) committee recently proposed a new risk stratification system for endometrial carcinoma (EC) patients that incorporates clinicopathologic and molecular features. The aim of the study is to compare the new ESGO/ESTRO/ESP risk classification system with the previous 2016 recommendations, evaluating the impact of molecular classification and defining a new algorithm for selecting cases for molecular analysis to assign the appropriate risk class.MethodsThe cohort included 211 consecutive EC patients. Immunohistochemistry and next-generation sequencing were used to assign molecular subgroups of EC: POLE mutant (POLE), mismatch repair deficient (MMRd), p53 mutant (p53abn), and no specific molecular profile (NSMP).ResultsImmuno-molecular analysis was successful in all cases, identifying the four molecular subgroups: 7.6% POLE, 32.2% MMRd, 20.9% p53abn, and 39.3% NSMP. The recent 2020 guidelines showed a 32.7% risk group change compared with the previous 2016 classification system: the reassignment is due to POLE mutations, abnormal p53 expression, and a better definition of lymphovascular space invasion. The 2020 system assigns more patients to lower-risk groups (42.2%) than the 2016 recommendation (25.6%). Considering the 2020 risk classification system that includes the difference between “unknown molecular classification” and “known,” the integration of molecular subgroups allowed 6.6% of patients to be recategorized into a different risk class. In addition, the use of the proposed algorithm based on histopathologic parameters would have resulted in a 62.6% reduction in molecular analysis, compared to applying molecular classification to all patients.ConclusionApplication of the new 2020 risk classification integrating clinicopathologic and molecular parameters provided more accurate identification of low-and high-risk patients, potentially allowing a more specific selection of patients for post-operative adjuvant therapy. The proposed histopathologic algorithm significantly decreases the number of tests needed and could be a promising tool for cost reduction without compromising prognostic stratification.

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“…We also compared risk group outcomes with and without molecular knowledge and confirmed distinct outcomes for the five risk groups with both approaches 56. With NSMP as the reference subgroup, p53 abn was associated with poor disease-specific survival within clinicopathologic low-risk carcinomas (HR: 9.1, 95% CI 2.0 to 41; p=0.004).…”

Section: Treatment Responsementioning

confidence: 66%

“…To assess the frequency of shift between risk groups with integration of molecular classification, we comprehensively classified 515 endometrial carcinomas into ESGO–ESTRO–ESP clinicopathologic and molecular integrated risk groups 56. Molecular classification caused a risk group shift in 38 patients (7.4%).…”

Section: Treatment Responsementioning

confidence: 99%

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Molecular classification of endometrial carcinoma: a clinically oriented review

2022

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The Cancer Genome Atlas research network performed a genome-wide analysis of endometrial carcinomas in 2013 and classified tumours into four distinct subgroups: polymerase-ϵ ultramutated, microsatellite unstable hypermutated, copy-number low and copy-number high. These molecular alterations are mostly mutually exclusive as only about 3% of tumours exhibit more than one molecular signature. Apart from the polymerase-ϵ ultramutated subgroup, molecular classification can be reproduced by using surrogate markers. This has facilitated the implementation of molecular diagnostics into routine patient care. Molecular subgroups are associated with different prognoses; thus, improved risk assessment is their most obvious clinical application. However, based on their unique molecular architectures, molecular subgroups should not be regarded simply as risk groups but rather as distinct diseases. This has prompted us and others to examine the role of molecular subgroups in modifying the prognostic effect of traditional risk factors, including clinical factors, uterine factors and tissue biomarkers, and in predicting the response to adjuvant therapies. In the following review, we summarise the current knowledge of molecularly classified endometrial carcinoma and present, based on our own experience, a proposal for implementing molecular classification into daily practice in pathology laboratories.

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Clinicopathologic vs. Molecular Integrated Prognostication of Endometrial Carcinoma by European Guidelines

Cited by 12 publications

References 18 publications

A novel algorithm to implement the molecular classification according to the new ESGO/ESTRO/ESP 2020 guidelines for endometrial cancer

A novel algorithm to implement the molecular classification according to the new ESGO/ESTRO/ESP 2020 guidelines for endometrial cancer

Integrated clinicopathologic and molecular analysis of endometrial carcinoma: Prognostic impact of the new ESGO-ESTRO-ESP endometrial cancer risk classification and proposal of histopathologic algorithm for its implementation in clinical practice

Molecular classification of endometrial carcinoma: a clinically oriented review

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