Genetic and molecular subtype heterogeneity in newly diagnosed early- and advanced-stage endometrial cancer

Paula, Arnaud Da Cruz; DeLair, Deborah F.; Ferrando, Lorenzo; Fix, Daniel; Soslow, Robert A.; Park, Kay J.; Chiang, Sarah; Reis‐Filho, Jorge S.; Zehir, Ahmet; Donoghue, Mark T.A.; Wu, Michelle; Brown, David; Murali, Rajmohan; Friedman, Claire F.; Zamarin, Dmitriy; Makker, Vicky; Mueller, Jennifer J.; Leitao, Mario M.; Abu‐Rustum, Nadeem R.; Aghajanian, Carol; Weigelt, Britta

doi:10.1016/j.ygyno.2021.02.015

Cited by 25 publications

(25 citation statements)

References 41 publications

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“…Even here, 29 MMRd cases were judged to be non endometrioid. The results indicate that using histologic subtype to attempt to “triage” cases to molecular subgroups may lead to significant problems with classification and suggest that markers should be applied independent of histology, this was also confirmed in the resent publication by Weigelt et al[25]. Applying TP53 immunohistochemistry on all cases of endometrioid FIGO 1 and 2 would represent a significant change for most pathology labs[26].…”

Section: Discussionmentioning

confidence: 75%

Implementation of the 2021 molecular ESGO/ESTRO/ESP risk groups in endometrial cancer

Imboden

Nastic

Ghaderi

et al. 2021

Preprint

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Introduction In 2021, a joint ESGO/ESTRO/ESP committee updated their evidence-based guidelines for endometrial cancer, recommending a new risk grouping incorporating both clinicopathologic and molecular parameters. We applied the new risk grouping and compared the results to those of the prior 2016 clinicopathologic system. Materials and methods We classified molecularly a cohort of 604 women diagnosed with endometrial cancer using immunohistochemistry for TP53 and MMR proteins on a tissue microarray, as well as Sanger sequencing for POLE mutations. These results, combined with clinicopathologic data, allowed the patients to be risk grouped using both the new 2021 molecular/clinicopathologic parameters and the prior 2016 clinicopathologic system. In addition, clinical treatment and outcome data were collected from medical records. Results The application of the 2021 molecular markers shows Kaplan-Meier curves with a significant difference between the groups for all survival. Molecular classification under the 2021 guidelines revealed a total of 39 patients (39/594, 7%) with a change in risk group in relation to the 2016 classification system: the shift was alone due to either P53abn or POLEmut molecular marker. In order to ensure correct 2021 molecular risk classification, not all patients with endometrial cancer need a molecular diagnostic: 386 (65.0%) cases would need to be analyzed by TP53 IHC, only 44 (7.4%) by MMR IHC and 109 (18.4%) POLE sequencing reactions. Conclusion Application of the 2021 molecular risk groups is feasible and shows significant differences in survival. IHC for TP53 and MMR and applying POLE sequencing is only needed in selected

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Section: Discussionmentioning

confidence: 75%

Implementation of the 2021 molecular ESGO/ESTRO/ESP risk groups in endometrial cancer

Imboden

Nastic

Ghaderi

et al. 2021

Preprint

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“…In this regard, a recent study by Faber et al found that high-grade type I endometroid cancer patients, analyzed separately from low-grade type I endometrioid tumor patients, resembled type II tumors, regarding their association with BMI and obesity [ 33 ]. In this specific category of patients (high-grade ECs), an analysis of the whole tumor genomic profile becomes mandatory, as it has been highlighted that some of these patients show peculiar molecular alterations, mainly of the AKT/PI3K/mTOR pathways and the PIK3CA gene, which may open new therapeutic perspectives [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Correlation of Leptin, Proinflammatory Cytokines and Oxidative Stress with Tumor Size and Disease Stage of Endometrioid (Type I) Endometrial Cancer and Review of the Underlying Mechanisms

Madeddu

Sanna

Gramignano³

et al. 2022

Cancers

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Endometrioid endometrial cancer is associated with increased BMI and obesity through multiple pathogenetic mechanisms involving hyperestrogenism, hyperinsulinemia, altered adipokine secretion, inflammation, and oxidative stress. In the present study, we aimed to investigate the correlation between BMI, leptin, the proinflammatory cytokines IL-6 and TNFα, reactive oxygen species (ROS), and the traditional prognostic factors T, G, N and M status among type I endometrioid and type II endometrial cancer patients. We enrolled 305 consecutive endometrial cancer patients prospectively. We found that BMI, leptin, and IL-6 significantly correlated with T status, N status, and M status among endometrioid type I endometrial cancer patients. Among type II endometrial cancer patients, BMI and leptin did not correlate with any of the prognostic parameters, whereas there was a positive correlation between IL-6 and the presence of distant metastases. In the multivariate regression analysis, BMI, leptin, and IL-6 were independent predictive variables of T, N, and M status in endometrioid type I endometrial cancer patients. Our study demonstrates that weight gain, adiposity-related adipokines, inflammation, and oxidative stress correlate with the prognostic factors of endometrioid endometrial cancer. Knowledge of the role of obesity-related biological pathways and mediators in the pathogenesis and prognosis of endometrioid endometrial malignancies may offer new perspectives on combined therapeutic strategies that have not been explored to date, both in the advanced disease and in the adjuvant setting.

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“…Even here, 29 MMRd cases were judged to be non endometrioid. The results indicate that using histologic subtype to attempt to "triage" cases to molecular subgroups may lead to significant problems with classification and suggest that markers should be applied independent of histology, which was also confirmed in the resent publication by Weigelt et al [25]. Applying TP53 immunohistochemistry on all cases of endometrioid FIGO 1 and 2 would represent a significant change for most pathology labs [26].…”

Section: Discussionmentioning

confidence: 61%

Implementation of the 2021 molecular ESGO/ESTRO/ESP risk groups in endometrial cancer

Imboden

Nastic

Ghaderi

et al. 2021

Gynecologic Oncology

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show abstract

Genetic and molecular subtype heterogeneity in newly diagnosed early- and advanced-stage endometrial cancer

Cited by 25 publications

References 41 publications

Implementation of the 2021 molecular ESGO/ESTRO/ESP risk groups in endometrial cancer

Implementation of the 2021 molecular ESGO/ESTRO/ESP risk groups in endometrial cancer

Correlation of Leptin, Proinflammatory Cytokines and Oxidative Stress with Tumor Size and Disease Stage of Endometrioid (Type I) Endometrial Cancer and Review of the Underlying Mechanisms

Implementation of the 2021 molecular ESGO/ESTRO/ESP risk groups in endometrial cancer

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