Ongoing Projects

Endocannabinoids system (ECS) in endometriosis

The cannabinoid receptor CB1 is located on sensory fibers that innervate the ectopic growths suggesting that the ECS modulates pain by acting locally in the peritoneal cavity. We have quantified the levels of endocannabinoids in serums and peritoneal fluids and identified 2-AG as a possible modulator of pain in endometriosis. (Andrieu T. et al. PAIN. 2021)

Epithelial to mesenchymal transition (EMT) in endometriosis

During the process of EMT, epithelial cells acquire features of mesenchymal cells affecting their proliferation, migration and infiltration rates. The main EMT marker, N-cadherin, has been detected in epithelial cells of a majority of the ectopic tissue. Interestingly, cells that went through this transition were also lacking the progesterone receptor. This result was recapitulated in vitro in endometrial carcinoma cell line. Our study has identified an important link between EMT and progesterone resistance in line with the pathogenesis of endometriosis. (Lijuan M. et al. SBMB. 2021)

Molecular diagnostics are evolving in endometrial cancer.

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. In our multi-center cohort of patients with molecular diagnosed endometrial cancer we applied the new risk grouping and compared the results to those of the prior 2016 clinicopathologic system. We found that the application of the 2021 molecular risk groups is feasible and shows significant differences in survival. The change in risk groups is given by TP53 and POLE mutations.  IHC for TP53 and MMR and applying POLE sequencing is only needed in selected cases and leads to shifting risk groups both upward and downward for a sizeable number of patients. It is possible to significantly reduce the number of analyses required to implement the classification if resources are limited. (Imboden S. Siegenthaler F. et al, Gynecologic Oncology, 2021)

Endometrial cancer (EmCa) with sentinel lymphnode dissection

In early-stage EmCa sentinel lymph node removal offers a convincing balance between oncological safety and perioperative morbidity. However, lymphovascular space invasion may represent a risk factors for recurrence and therefore prior lymph-node evaluation is crucial. (Imboden S. et al. Eur J Surg Oncol. 2019)

POLE-mutated endometrial cancer (EmCa)

By analyzing molecular markers for EmCa, we could demonstrate that mutations in the exonuclease domain of the DNA polymerase epsilon (POLE) gene is significantly associated with previously unknown clinicopathological characteristics. Especially, when considering hotspot mutations, prognosis for patients with mutation was significantly better in comparison with patients with non-mutated tumours. (Imboden S. et al. PLoS One. 2019)

Circulating tumor DNA in endometrial cancer

Analysis of circulating tumor DNA (ctDNA) has evolved as a promising technique with important clinical significance. The assessment of blood sample for the presence, level, and composition of ctDNA may enable monitoring of responses to treatment, assessment of treatment resistance, and detection of post-surgical residual disease, in order to identify patients at high risk of recurrence. The aim of our research project is to analyze ctDNA in endometrial cancer patients. (Siegenthaler F.)

Progesterone resistance in endometriosis

Dienogest is one of the promising options for the long-term hormonal management of endometriosis. By analyzing the prevalence of somatic mutations, cellular composition, or transcriptomic profile between endometriotic lesions from non-responders, we intend to unveil the mechanism of Dienogest resistance which occurs in several patients. (Nirgianakis K., McKinnon B., Škrabalová J.)

Endometrial cell atlas revealed by single-cell analysis.

Endometriosis is a frequently occurring disease affecting 1 in 10 women, characterized by the growth of endometrial tissue outside the uterus. We aim to unveil disease causing changes in endometrial cellular pathways and cell interactions using cutting-edge single-cell techniques to gain a better understanding of the disease and its origin. (Duempelmann L.)

Clinical and molecular predictors for long overall survival of patients with high grade serous ovarian cancer (HGSC)

Genomic and immune determinants of long-term survival are analysed in HGSC long-term survivors (OS ≥8years) and short- to mid- term survivors (OS 2-7years) using multiplexed immunohistochemistry and next generation DNA and RNA sequencing of patient tumor samples. Clinical and epidemiological factors contributing to exceptional survival are investigated further as part of an international multicentre trial. (Saner F.)