Early-stage endometrial cancer, CTNNB1 mutations, and the relationship between lymphovascular space invasion and recurrence.

Imboden, Sara; Tapia, Coya; Scheiwiller, Nadja; Kocbek, Vida; Altermatt, Hans J; Janzen, Jan; Mueller, Michael D.; Mc Kinnon, Brett (2020). Early-stage endometrial cancer, CTNNB1 mutations, and the relationship between lymphovascular space invasion and recurrence. Acta obstetricia et gynecologica Scandinavica, 99(2), pp. 196-203. Wiley-Blackwell 10.1111/aogs.13740

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INTRODUCTION Women diagnosed with early-stage (FIGO 1) endometrial cancer, grade 1 and 2 can have a good prognosis. Most of these women can be treated successfully with a hysterectomy and bilateral salpingo-oophorectomy and without the additional adjuvant treatment that is accompanied by more risks for complications. However, when recurrence does occur, the consequences can be dire. Accurate decisions must therefore be made by surgeons to avoid either under- or over-treatment. Risk and patient stratification for tailoring treatment still need further improvement. Both histopathology and genetic variants could be integrated into the decision process if relevant factors were identified. MATERIAL AND METHODS Morphological features and the presence of selected genetic mutations in isolated malignant endometrial epithelial cells from these tumors were analyzed in a strictly defined cohort of FIGO 1, grade 1 and 2 low-risk endometrial cancer. Their presence in this cohort, their relationship to recurrence, and the association between histopathological features and mutations were determined. This analysis was performed using archival formalin-fixed paraffin-embedded tissue, complete re-evaluation of histopathological features, laser capture microdissection of epithelial cells, and a polymerase chain reaction-based mutational screening assay. RESULTS Twenty-one women with recurrence, after initial identification as low-risk endometrial cancer, were compared with 20 matched control women. The histological marker of lymphovascular invasion was significantly associated with recurrence. There was also a very high prevalence of mutations in CTNNB1 gene, occurring in 50% of this cohort. PTEN mutations were also observed in 27.8% of cases and PIK3CA mutations in 22.2%; none of these mutations were significantly related to recurrence. CONCLUSIONS This study supports the importance of lymphovascular space invasion to identify women with significant risk for recurrence in initially low-risk, early-stage endometrial cancer. It also identifies CTNNB1 as a significant mutation in early-stage disease, and although it may not represent a marker for recurrence its high prevalence in early stage disease could have relevance for both pathogenesis and early treatment.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology

UniBE Contributor:

Imboden, Sara; Mueller, Michael and Mc Kinnon, Brett

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0001-6349

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Monika Zehr

Date Deposited:

24 Dec 2019 11:43

Last Modified:

20 Jan 2020 01:33

Publisher DOI:

10.1111/aogs.13740

PubMed ID:

31562818

Uncontrolled Keywords:

CTNNB1 endometrial cancer genetic mutation histopathology low risk lymphovascular space invasion recurrence

BORIS DOI:

10.7892/boris.136446

URI:

https://boris.unibe.ch/id/eprint/136446

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