Obstetrics and Gynaecology - Theses
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ItemCharacterisation of endometriotic lesions( 2021)Endometriosis is a common gynaecological disease where “endometrial-like” tissue forms ectopic lesions, most commonly in the pelvis. The disease affects 11% of reproductive-aged women within their lifetime, and presents with a range of symptoms, often including pelvic pain. Surgical and medical treatments aimed at reducing symptoms can have limited effectiveness, side effects and patient-to-patient variability. While some patients respond well to treatment there is no ‘one shoe fits all’ approach to managing endometriosis. Endometriotic lesions are the characteristic feature diagnostic of endometriosis and variable macroscopic and microscopic lesion appearances have been observed. Despite this heterogeneity, features beyond the presence/absence of endometrial-like glands and/or stroma are not factored into diagnosis. Additionally, existing endometriosis classification systems are based on surgical observations and do not predict treatment responsiveness or disease prognosis. This is unlike other pathologies (e.g. gynaecological cancers) where an array of disease characteristics are factored in to diagnosis to guide treatment decisions and predict outcomes. The identification of distinct endometriotic lesion subtypes that relate to clinical outcomes would be invaluable to improving treatment for endometriosis patients. The objective of this thesis was to characterise specific microscopic features of superficial peritoneal endometriotic lesions including histological and immunohistochemical characteristics such as collagen, smooth muscle, leukocytes, steroid receptors, proliferative markers, innervation, and vasculature. Studies aimed to determine if distinct subtypes of lesions exist based on these features. These studies also aimed to determine if endometriotic lesions exhibit patterns in these features based on menstrual cycle phase and if these patterns reflected those of matched eutopic endometrium. Based on the histological features and tissue and cell types analysed, there was considerable heterogeneity in the appearance of superficial peritoneal endometriotic lesions, even within individual patients and single biopsies. For example, the presence and/or morphology of collagen, smooth muscle, and immune cells adjacent to these lesions was diverse and, in some cases, varied based on biopsy location. The heterogeneity in lesion appearances, particularly within an individual biopsy or single patient, presents a challenge to identifying distinct lesion subtypes that could aid improvements to endometriosis classification and patient stratification. Only a subset of endometriotic lesions displayed histological and immunohistochemical features associated with the menstrual cycle phase. Where there were menstrual cycle-related patterns in histological features and steroid receptor expression, these diverged from those of the matched eutopic endometrium. There may be few similarities between endometriotic lesions and the endometrium beyond the observation of “endometrial-like” glands and stroma. Consequently, future endometriosis studies should shift focus and be wary of simply comparing endometriotic lesions with eutopic endometrium when it may be more appropriate to study endometriotic lesions independently. To improve patient treatment outcomes, future studies should investigate the contribution of endometriotic lesions to disease pathophysiology and potential therapeutic targets. The findings of this thesis suggest research should focus on determining if the diversity of lesion appearance relates to variable steroid hormone responsiveness, stages of disease progression, lesion location and other potential aspects of disease pathophysiology.