lecular and biological nature of endometrial cancer

PhD ceremony: Ms. R.A. de Jong, 14.30 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Molecular and biological nature of endometrial cancer

Promotor(s): prof. H.W. Nijman, prof. H. Hollema, prof. I.P. Kema

Faculty: Medical Sciences

Endometrial carcinoma is a heterogeneous disease with several histological types and different biological behavior. The general prognosis for endometrial carcinoma is good, but in patients diagnosed with non-endometrioid subtypes such as serous carcinoma, clearcell carcinoma or carcinosarcomas, life-expectancy decreases dramatically. Especially in these patients, the development of new treatment modalities is warranted to improve prognosis.

Immunotherapy is an interesting new treatment option where it is generally recognized that the immune system has an important role in regulating cancer development and progression. The research presented in this thesis shows that the immune system has a significant role in endometrial carcinoma. However, several mechanisms facilitate cancer cells to escape from immune-mediated recognition and killing by the immune system. In-depth knowledge of escape mechanisms is essential to design an (effective) immunotherapy-based treatment modality. This thesis demonstrated that escape mechanisms are present in endometrial carcinoma and significantly influence prognosis. Using this knowledge, it may become feasible to predict which patients will benefit from immunotherapeutic strategies. In addition to the identification of new treatment modalities, we also aim for improvement of standard treatment modalities. Currently, patients with high-risk endometrial carcinoma are treated with surgery and adjuvant external beam radiotherapy. Radiotherapy is associated with short and long-term morbidity and should therefore merely be used in patients who will benefit most. Our research shows that gastrointestinal symptoms are reduced when patients with high-risk endometrial carcinoma and without lymph-node metastases after adequate surgical staging, are treated with external beam radiotherapy that is limited to a small pelvic field as compared to a standard pelvic field treatment.