Endometriosis and Gynaecological Oncology
Endometriosis and inflammation (Group leader: Prof. Dr. Nick A. Bersinger, PhD)
Endometriosis is an extremely prevalent condition that is accompanied by chronic pain, reduced fecundity and an increased risk of ovarian cancer later in life – all of which can be related to inflammation. The most widely accepted theory of endometriotic lesion development is retrograde menstruation, a process by which viable endometrial cells are refluxed backwards into the peritoneal cavity. These cells attach to the underlying tissue and via a hormonal and inflammatory stimulation continue to grow. As retrograde menstruation has been shown to occur in almost 90% of women additional factors must be involved that support the attachment of the endometrial tissue in those patients who suffer endometriosis.
We are studying the presence of pro- and anti-inflammatory cytokines, angiogenic, neurogenic, and growth factors in the peritoneum at both the gene expression and functional protein level. Transcriptional investigations (RT and Q-PCR on the above marker genes) are performed with RNA obtained from fresh endometrial tissue. At the protein level immunohistochemistry and Western blot analyses are performed on both eutopic (intra-uterine) and ectopic (extra-uterine endometriotic lesion) tissue as well as on peritoneal fluid (PF) collected from the peritoneal cavity (cul-de-sac = pouch of Douglas) during the laparoscopic intervention. Various inflammatory cytokines and growth factors are determined in the PF by microplate immunoassays using either manual ELISA protocols (commercial or developed in our laboratory) or the new multiplexed double fluorescence (x-map) technology based assays on the Bio-Rad Bioplex® platform.
The results are set in relation to the clinical situation such as the presence, frequency and intensity of pain (dysmenorrhoea, lower abdominal pain, and dyspareunia), fertility, the use of medicines, and the risk of developing ovarian cancer later in life. Cultures of endometrial cell lines and of primary endometrial cells (epithelial and stromal) are used as models for studying cytokine, angiogenic and neuro-stimulatory marker production in vitro after stimulation by hormones and growth factors. Using tissue obtained form archived endometriotic lesions removed during laparoscopy we are analysing the activation of a newly identified signalling pathway (mediated through mTOR) that links inflammation to angiogenesis, a vital step in both endometriosis and malignant lesion development (see below).
Gynaecological Oncology (Group leader: Dr. Brett McKinnon, PhD)
Ovarian cancer is the most lethal gynaecological carcinoma and the fifth most common cause of all cancer deaths. Due to ineffective screening methods and almost no early clinical symptoms 75 % of ovarian tumours are diagnosed at an advanced stage resulting in fewer than 20 % of women surviving long term. If however, the tumours are detected early survival rates can exceed 90 %. An association between endometriosis and ovarian cancer has been established. Although the risk remains small why some lesions progress to malignancy is not clear. Understanding the mechanisms that lead to progression may provide some clues towards establishing an early diagnosis. We are therefore interest in the inflammatory microenvironment created by endometriosis and the signal transduction pathways that it activates to determine if these conditions can stimulate the progression from a benign to malignant lesion.
Endometrial cancer is the most common gynaecological malignancy and the fourth most common malignancy in women. If detected early the prognosis is good, but if recurrence occurs the survival time is barely 12 months. All cases of endometrial cancer are currently treated by surgery. The extent of surgery however is still controversial. When should lymph nodes be removed? There is currently the danger of under treatment of high risk tumors and the over treatment of low risk tumors. We wish to therefore address this treatment gap by developing an improved surgical lymph node biopsy technique accompanied with molecular biological methods to improve the identification of metastatic tissue. Furthermore we also aim to improve the screening of women at risk by identifying specific genetic risk factors that may predispose women to endometrial cancer recurrence.