Prognostic value of the TCGA molecular classification in uterine carcinosarcoma

Travaglino, Antonio; Raffone, Antonio; Raimondo, Diego; Arciuolo, Damiano; Angelico, Giuseppe; Valente, Michele; Scaglione, Giulia; D’Alessandris, Nicoletta; Casadio, Paolo; Inzani, Frediano; Mollo, Antonio; Santoro, Angela; Seracchioli, Renato; Zannoni, Gian Franco

doi:10.1002/ijgo.13937

Cited by 30 publications

(31 citation statements)

References 45 publications

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“…5 Regarding the MSI/MMRd cases, a reduced sensitivity to chemotherapy has been reported, probably due to the progressive accumulation of mutations 5,36 ; in CCC, the MSI/ MMRd signature appears associated with improved prognosis, 34 while this is still not confirmed in UCS. 35 All of these hypotheses need to be tested in prospective studies.…”

Section: Discussionmentioning

confidence: 99%

Uterine carcinosarcoma vs endometrial serous and clear cell carcinoma: A systematic review and meta‐analysis of survival

Raffone

Travaglino

Raimondo

et al. 2021

Intl J Gynecology & Obste

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Background: It is unclear whether uterine carcinosarcoma (UCS) is more aggressive than endometrial serous carcinoma (SC) and clear cell carcinoma (CCC). Objectives:To compare the prognosis of UCS to that of endometrial SC and CCC, through a systematic review and meta-analysis.Methods: Four electronic databases were searched from January 2000 to October 2020. All studies assessing hazard ratio (HR) for death in UCS vs SC and/or CCC. HRs for death with 95% confidence interval were extracted and pooled by using a randomeffect model. A significant P-value <0.05 was adopted.Results: Six studies with 11 029 patients (4995 with UCS, 4634 with SC, 1346 with CCC and 54 with either SC or CCC) were included. UCS showed a significantly worse prognosis than SC/CCC both overall (HR = 1.51; P = 0.008) and at early stage (HR = 1.58; P < 0.001). Similar results were found for UCS vs SC (HR = 1.53; P < 0.001) and UCS vs CCC (HR = 1.60; P < 0.001).Conclusions: Compared to SC and CCC, UCS has a significantly worse prognosis, with a 1.5-1.6-fold increased risk of death. This might justify a more aggressive treatment for UCS compared to SC and CCC. Further studies are necessary to define the prognostic impact of different molecular subgroups.

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Section: Discussionmentioning

confidence: 99%

Uterine carcinosarcoma vs endometrial serous and clear cell carcinoma: A systematic review and meta‐analysis of survival

Raffone

Travaglino

Raimondo

et al. 2021

Intl J Gynecology & Obste

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“…Therefore, POLE mutations prognostically supersede both MMR deficiency and p53 mutations [ 4 , 10 , 36 ]. Even histotype seems to have no value in the case of POLE mutation, since POLE-mutant non-endometrioid ECs still show a good prognosis [ 9 , 18 , 37 , 38 , 39 ]. The mutational load itself causes a strong immune response due to the exposition of many neoantigens, which is reflected in a lymphocytic infiltration that accompanies most (~79%) POLE-mutant ECs and could be responsible for their good prognosis [ 13 , 40 ].…”

Section: Pole-mutatedmentioning

confidence: 99%

TCGA Molecular Prognostic Groups of Endometrial Carcinoma: Current Knowledge and Future Perspectives

Arciuolo

Travaglino

Raffone

et al. 2022

IJMS

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The four TCGA-based molecular prognostic groups of endometrial carcinoma (EC), i.e., POLE-mutant, mismatch repair (MMR)-deficient, p53-abnormal, and “no specific molecular profile” (NSMP), have recently been integrated into ESGO-ESTRO-ESP guidelines. The POLE-mutant and MMR-deficient groups are associated with high mutational load, morphological heterogeneity, and inflammatory infiltration. These groups are frequent in high-grade endometrioid, undifferentiated/dedifferentiated, and mixed histotypes. POLE-mutant ECs show good prognosis and do not require adjuvant treatment, although the management of cases at stage >II is still undefined. MMR-deficient ECs show intermediate prognosis and are currently substratified based on clinicopathological variables, some of which might not have prognostic value. These groups may benefit from immunotherapy. P53-mutant ECs are typically high-grade and often morphologically ambiguous, accounting for virtually all serous ECs, most carcinosarcomas and mixed ECs, and half of clear-cell ECs. They show poor prognosis and are treated with chemoradiotherapy; a subset may benefit from HER2 inhibitors or PARP inhibitors. The NSMP group is the most frequent TCGA group; its prognosis is highly variable and affected by clinicopathological/molecular factors, most of which are still under evaluation. In conclusion, the TCGA classification has improved diagnosis, risk stratification, and management of EC. Further studies are needed to resolve the points of uncertainty that still exist.

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“…Although most MMRd ECs are endometrioid, they are also known for their intratumoral heterogeneity in which clear cell and serous-like features can be dominant. In addition, approximately one-third of the DDECs/UECs are reported to be MMRd, 23 and recent reports have also highlighted that CSs can also be MMRd, albeit in low frequencies 24–26 . Based on this and the established high interobserver variability of diagnosing nonendometrioid subtypes upon H&E, it is difficult to defend a histotype-directed MMR-testing algorithm.…”

Section: The Strengths and Weaknesses Of The Molecular Classificationmentioning

confidence: 99%

“…In addition, approximately one-third of the DDECs/UECs are reported to be MMRd, 23 and recent reports have also highlighted that CSs can also be MMRd, albeit in low frequencies. [24][25][26] Based on this and the established high interobserver variability of diagnosing nonendometrioid subtypes upon H&E, it is difficult to defend a histotype-directed MMR-testing algorithm. Therefore, the author recommends histotype/grade-agnostic universal testing of MMR status, independent of age, following the recommendations of the European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology.…”

Section: The Strengths and Weaknesses Of The Molecular Classificationmentioning

confidence: 99%

The Best of Both Worlds: Combining the Molecular and Traditional (Histotype/Grade) Endometrial Cancer Classification

Bosse¹

2022

AJSP: Reviews and Reports

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The discovery of 4 distinct molecular endometrial cancer subgroups by The Cancer Genome Atlas has fundamentally changed the way we look at endometrial carcinoma today. The proven robustness of surrogate markers in a diagnostic algorithm endorsed by the World Health Organization classification of female genital tumors 2020 has opened the gates for worldwide implementation. This advance delivers a reproducible classification system with improved prognostication and a biological basis for future targeted treatments. Although we all embrace this exciting development, we now struggle how to position the traditional histology-based classification (histotype/International Federation of Gynecology and Obstetrics grade). The author discusses the strengths, weaknesses, opportunities, and threats and deliberates on how we could bring the best of both worlds together.

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Prognostic value of the TCGA molecular classification in uterine carcinosarcoma

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 30 publications

References 45 publications

Uterine carcinosarcoma vs endometrial serous and clear cell carcinoma: A systematic review and meta‐analysis of survival

Uterine carcinosarcoma vs endometrial serous and clear cell carcinoma: A systematic review and meta‐analysis of survival

TCGA Molecular Prognostic Groups of Endometrial Carcinoma: Current Knowledge and Future Perspectives

The Best of Both Worlds: Combining the Molecular and Traditional (Histotype/Grade) Endometrial Cancer Classification

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