48 A local study on survival outcome and prognostic significance of lower uterine segment involvement in early stage endometrioid endometrial carcinoma

Abstract Background In the last years, mutations in the exon 3 of CTNNB1 have emerged as a possible prognostic factor for recurrence in early stage endometrioid endometrial carcinoma, especially in cases with no specific molecular profile (NSMP). Objective To define the prognostic value of CTNNB1 mutations in early stage endometrioid endometrial carcinoma, through a systematic review and meta-analysis. Methods Electronic databases were searched from their inception to November 2020 for all studies assessing the prognostic value of CTNNB1 mutation in early stage (FIGO I–II) endometrioid endometrial carcinoma. Odds ratio (OR) for tumor recurrence and hazard ratio (HR) for disease-free survival (DFS) were calculated with a significant p value < 0.05. Results Seven studies with 1031 patients were included. Four studies were suitable for meta-analysis of OR and showed significant association between CTNNB1 mutation and the absolute number of recurrence (OR = 3.000; p = 0.019); the association became stronger after excluding patients with known molecular status other than NSMP (HR = 5.953; p = 0.012). Three studies were suitable for meta-analysis of HR and showed no significant association between CTNNB1 mutation and decreased DFS (HR = 1.847; p = 0.303); the association became significant after excluding patients with known molecular status other than NSMP (HR = 2.831; p = 0.026). Conclusion CTNNB1 mutation is significantly associated with recurrence in early stage endometrioid endometrial carcinomas, especially in the NSMP, appearing potentially useful in directing adjuvant treatment.

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Lower Uterine Segment Involvement is Associated with Poor Outcomes in Early-Stage Endometrioid Endometrial Carcinoma

Annals of Surgical Oncology ◽

10.1245/s10434-010-1454-9 ◽

2010 ◽

Vol 18 (5) ◽

pp. 1419-1424 ◽

Cited By ~ 13

Author(s):

Nora T. Kizer ◽

Feng Gao ◽

Saketh Guntupalli ◽

Premal H. Thaker ◽

Matthew A. Powell ◽

...

Keyword(s):

Endometrial Carcinoma ◽

Early Stage ◽

Lower Uterine Segment ◽

Endometrioid Endometrial Carcinoma ◽

Poor Outcomes

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Complete Clinical Response in Stage IVB Endometrioid Endometrial Carcinoma after First-Line Pembrolizumab Therapy: Report of a Case with Isolated Loss of PMS2 Protein

Case Reports in Oncology ◽

10.1159/000510000 ◽

2020 ◽

Vol 13 (3) ◽

pp. 1067-1074

Author(s):

Jesus Paula Carvalho ◽

Auro Del Giglio ◽

Maria Isabel Achatz ◽

Filomena Marino Carvalho

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Endometrial Carcinoma ◽

Early Stage ◽

Gynecological Cancer ◽

Stage Iv ◽

Protein Loss ◽

First Line ◽

Early Stage Disease ◽

Endometrioid Endometrial Carcinoma

Endometrial cancer is the only gynecological cancer that is rising in incidence and associated mortality worldwide. Although most cases are diagnosed as early stage disease, with chances of cure after primary surgical treatment, those with advanced or metastatic disease have a poor prognosis because of the quality of treatment options that are currently available. Mismatch repair (MMR)-deficient cancers are susceptible to programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 inhibitors. The US Food and Drug Administration granted accelerated approval to pembrolizumab for MMR-deficient tumors, the first tumor-agnostic approval for a drug. We present a case of stage IV endometrioid endometrial carcinoma with isolated PMS2 protein loss, in which treatment with first-line pembrolizumab therapy achieved a complete clinical and pathological response of tumor.

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Tumor progression, metastasis, and modulators of epithelial–mesenchymal transition in endometrioid endometrial carcinoma: an update

Endocrine Related Cancer ◽

10.1530/erc-15-0218 ◽

2015 ◽

Vol 23 (2) ◽

pp. R85-R111 ◽

Cited By ~ 32

Author(s):

Annu Makker ◽

Madhu Mati Goel

Keyword(s):

High Risk ◽

Tumor Progression ◽

Endometrial Carcinoma ◽

Molecular Mechanisms ◽

Epithelial Mesenchymal Transition ◽

Current Knowledge ◽

Early Stage ◽

Invasion And Metastasis ◽

Mesenchymal Transition ◽

Endometrioid Endometrial Carcinoma

Endometrioid endometrial carcinoma (EEC), also known as type 1 endometrial cancer (EC), accounts for over 70–80% of all cases that are usually associated with estrogen stimulation and often develops in a background of atypical endometrial hyperplasia. The increased incidence of EC is mainly confined to this type of cancer. Most EEC patients present at an early stage and generally have a favorable prognosis; however, up to 30% of EEC present as high risk tumors, which have invaded deep into the myometrium at diagnosis and progressively lead to local or extra pelvic metastasis. The poor survival of advanced EC is related to the lack of effective therapies, which can be attributed to poor understanding of the molecular mechanisms underlying the progression of disease toward invasion and metastasis. Multiple lines of evidence illustrate that epithelial–mesenchymal transition (EMT)-like events are central to tumor progression and malignant transformation, endowing the incipient cancer cell with invasive and metastatic properties. The aim of this review is to summarize the current knowledge on molecular events associated with EMT in progression, invasion, and metastasis of EEC. Further, the role of epigenetic modifications and microRNA regulation, tumor microenvironment, and microcystic elongated and fragmented glands like invasion pattern have been discussed. We believe this article may perhaps stimulate further research in this field that may aid in identifying high risk patients within this clinically challenging patient group and also lead to the recognition of novel targets for the prevention of metastasis – the most fatal consequence of endometrial carcinogenesis.

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Early recurrence of early stage endometrioid endometrial carcinoma: Possible etiologic pathways and management options

Maturitas ◽

10.1016/j.maturitas.2014.04.009 ◽

2014 ◽

Vol 78 (3) ◽

pp. 155-159 ◽

Cited By ~ 1

Author(s):

Christos Iavazzo ◽

Ioannis D. Gkegkes ◽

Nikolaos Vrachnis

Keyword(s):

Endometrial Carcinoma ◽

Early Stage ◽

Early Recurrence ◽

Management Options ◽

Endometrioid Endometrial Carcinoma

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Myoinvasive Pattern as a Prognostic Marker in Low-Grade, Early-Stage Endometrioid Endometrial Carcinoma

Cancers ◽

10.3390/cancers11121845 ◽

2019 ◽

Vol 11 (12) ◽

pp. 1845 ◽

Cited By ~ 2

Author(s):

Ignacio Ruz-Caracuel ◽

Jorge L Ramón-Patino ◽

Álvaro López-Janeiro ◽

Laura Yébenes ◽

Alberto Berjón ◽

...

Keyword(s):

Prognostic Factor ◽

Microsatellite Instability ◽

Endometrial Carcinoma ◽

Early Stage ◽

Disease Free Survival ◽

Figo Stage ◽

Low Grade ◽

Gynecology And Obstetrics ◽

Endometrioid Endometrial Carcinoma ◽

Endometrial Carcinomas

Low-grade and early Federation for Gynecology and Obstetrics (FIGO) stage endometrioid endometrial carcinomas (EEC) have an excellent prognosis. However, approximately 10% of patients develop recurrence, which cannot be correctly predicted at diagnosis. We evaluated myoinvasive patterns as a prognostic factor of relapse in low-grade, early-stage EEC. Two-hundred and fifty-eight cases were selected according to the following inclusion criteria: (i) endometrioid endometrial carcinomas, (ii) grade 1 or 2 with (iii) FIGO stage I or II, and (iv) clinical follow-up. Slides were reviewed to annotate the myoinvasive pattern present in each case (infiltrative glands, microcystic, elongated and fragmented –MELF-, broad front, adenomyosis-like and adenoma malignum). Microsatellite instability was studied by immunoexpression of mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6). There were 29 recurrences (11.2%) among the 258 cases analysed. A predominant broad front myoinvasive pattern was significantly associated with tumour relapse (p = 0.003). The presence of a pattern of infiltrative glands (p = 0.001) and microsatellite instability (p = 0.004) were associated with lower disease-free survival, without having an impact on overall survival. Our observations suggest the potential value of the pattern of myoinvasion as a prognostic factor in low-grade, early-stage endometrioid endometrial carcinoma.

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