Clear cell endometrial carcinomas with mismatch repair deficiency have a favorable prognosis: A systematic review and meta-analysis

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

doi:10.1016/j.ygyno.2021.07.007

Cited by 26 publications

(36 citation statements)

References 44 publications

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“…33 On the other hand, UCS appears at significantly higher risk compared to the classical type II endometrial carcinomas, in agreement with our previous study. 34 Such a result was also confirmed on the subset of patients with early-stage disease (HR = 1.58).…”

Section: Discussionmentioning

confidence: 64%

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: 64%

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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“…In clear cell carcinoma, MSI/MMR-d is a favorable prognostic factor [36]. These apparent differences might be due to the fact that all MSI/MMR-d carcinomas tend to have an intermediate prognosis independently from morphology and other molecular markers, probably due to the high mutational load [37, 38]. However, in UDC/DDC, other factors (in particular the SWI/SNF complex proteins deficiency) seem to be more prognostically relevant than the MSI/MMR-d status [11].…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological Features Associated with Microsatellite Instability/Mismatch Repair Deficiency in Uterine Carcinosarcoma: A Quantitative Systematic Review

et al. 2022

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Introduction: Recent studies suggested that microsatellite instability/mismatch repair deficiency (MSI/MMR-d) might define a clinicopathologically distinct subset of uterine carcinosarcomas (UCSs). Objective: The aim of this study was to compare clinicopathological features between MSI/MMR-d and microsatellite-stable/mismatch repair-proficient (MSS/MMR-p) UCSs. Methods: A quantitative systematic review was performed by searching electronic databases from January 2000 to January 2021. All studies assessing MSI/MMR status in UCS were included. Odds ratio (OR) with a significant two-tailed p value <0.05 was used to assess the association of MSI/MMR-d with clinicopathological features. Results: Eleven studies with 783 patients were included. MSI/MMR-d was directly associated with endometrioid (pure: p < 0.001; pure + mixed: p < 0.001), undifferentiated/dedifferentiated (p < 0.001), and clear cell carcinoma component (p = 0.046), and inversely associated with age >60 (p = 0.034), serous carcinoma component (pure: p < 0.001; pure + mixed: p < 0.001), heterologous sarcoma component (p = 0.027), TP53-mutation/p53-abnormal expression (p < 0.001), and recurrence (p < 0.001). MSI/MMR-d showed no significant association with advanced FIGO stage (OR = 1.259; p = 0.517), low-grade carcinoma component (pure: p = 0.596; pure + mixed: p = 0.307), mixed carcinoma component (p = 1), and proportion of patients “dead of disease” (p = 0.352), “alive with disease” (p = 1) or with “no evidence of disease” (p = 0.458). Conclusion: MSI/MMR-d UCSs show younger age, more common endometrioid, undifferentiated or clear cell carcinoma component, and less common serous carcinoma component, heterologous sarcoma component, and TP53 mutation than MSS/MMR-p UCSs. Given the discrepancy between recurrence rate and oncologic outcomes at the last follow-up, further studies are necessary to define whether MSI/MMR-d UCSs have better prognosis.

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“…In fact, in high-grade carcinomas, MMR-deficient cases seem to have a better prognosis than NSMP cases [ 8 , 14 ]. Evidence in this regard has been found for clear cell carcinoma [ 40 ], mixed carcinomas [ 41 ], and carcinosarcoma [ 42 ]. Moreover, it has been suggested that all MMR deficient endometrial carcinomas may have a similar prognosis regardless of the histotype [ 8 ]; the only exception in this regard is represented by undifferentiated/dedifferentiated carcinoma, in which the immunohistochemical expression of SWI/SNF complex proteins seems to be more prognostically relevant than the MMR status [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

L1CAM Expression in Microcystic, Elongated, and Fragmented (MELF) Glands Predicts Lymph Node Involvement in Endometrial Carcinoma

Arciuolo

Travaglino

Santoro

et al. 2022

Cancers

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In endometrial carcinoma, both L1CAM overexpression and microcystic, elongated and fragmented (MELF) patterns of invasion have been related to epithelial-to-mesenchymal transition and metastatic spread. We aimed to assess the association between L1CAM expression, the MELF pattern, and lymph node status in endometrial carcinoma. Consecutive cases of endometrial carcinoma with MELF pattern were immunohistochemically assessed for L1CAM. Inclusion criteria were endometrioid-type, low-grade, stage T1, and known lymph node status. Uni- and multivariate logistic regression were used to assess the association of L1CAM expression with lymph node status. Fifty-eight cases were included. Most cases showed deep myometrial invasion (n = 42, 72.4%) and substantial lymphovascular space invasion (n = 34, 58.6%). All cases were p53-wild-type; 17 (29.3%) were mismatch repair-deficient. Twenty cases (34.5%) had positive nodes. No cases showed L1CAM positivity in ≥10% of the whole tumor. MELF glands expressed L1CAM at least focally in 38 cases (65.5%). L1CAM positivity in ≥10% of the MELF component was found in 24 cases (41.4%) and was the only significant predictor of lymph node involvement in both univariate (p < 0.001) and multivariate analysis (p < 0.001). In conclusion, L1CAM might be involved in the development of the MELF pattern. In uterine-confined, low-grade endometrioid carcinomas, L1CAM overexpression in MELF glands may predict lymph node involvement.

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Clear cell endometrial carcinomas with mismatch repair deficiency have a favorable prognosis: A systematic review and meta-analysis

Cited by 26 publications

References 44 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

Clinicopathological Features Associated with Microsatellite Instability/Mismatch Repair Deficiency in Uterine Carcinosarcoma: A Quantitative Systematic Review

L1CAM Expression in Microcystic, Elongated, and Fragmented (MELF) Glands Predicts Lymph Node Involvement in Endometrial Carcinoma

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