Marker discovery for response to (chemo) radiation and prognosis in cervical cancer

PhD ceremony: Ms. M.G. Noordhuis, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Title: Marker discovery for response to (chemo) radiation and prognosis in cervical cancer

Promotor(s): prof. A.G.J. van der Zee, prof. H. Hollema, prof. G. de Bock

Faculty: Medical Sciences

Cervical cancer is, after breast and colorectal cancer, the most common cancer among women. According to the stage of the disease patients are treated surgically (early stage) or with chemoradiation (advanced stage). The 5-year survival rate of patients treated with chemoradiation is 66%. Treatment is generally based on well-known clinicopathologic factors, such as disease stage and tissue examination. The aim of this thesis was to identify cell biological markers and pathways associated with pelvic lymph node metastasis, response to (chemo)radiation, and prognosis in cervical cancer.

The thesis provides validated insights in the molecular mechanism of lymph node metastases. In a large series of early stage cervical cancer patients, two pathways (TGF-β and the p120-associated β-catenin pathway) were associated with absence and presence of pelvic lymph node metastases, respectively. Positive PTEN immunostaining (member of EGFR-pathway) was also associated with absence of lymph node metastases. In addition, in a large series of advanced stage cervical cancer patients who were treated with (chemo)radiation, the EGFR-pathway and phosphorylated ATM were discovered as independent predictors of poor response to chemoradiation and poor survival. The results of this thesis may contribute to a better prediction of pelvic lymph node metastases and response to chemoradiation. Ideally, therapeutic targeting these pathways may lead to improved survival of cervical cancer patients.