OncoAfrica

Connecting the dots: Endometriosis and Ovarian Cancer. Is there a possible association?

Date: 30th September 2024 | Issue #2

The human endometrium (layer of tissue that lines the uterus) is a unique tissue that undergoes important changes during the menstrual cycle. Due to the exposure of different risk factors in a woman’s lifetime, normal endometrial tissue can give rise to multiple pathological conditions including endometriosis. The cause and disease mechanisms behind such conditions remain largely unclear. Endometriosis is a common, estrogen-dependent disease that affects ~20% of women of child-bearing age. It occurs when endometrial tissue grows outside the uterus mostly in the abdominal and pelvic cavity. The tissue may sometimes be found outside the pelvis such as in the lungs, gut, and brain. Most women with endometriosis experience chronic pelvic pain and infertility, which impacts their quality of life, reproductive function and causes a significant economic burden.

While endometriosis is considered a benign disease (non-malignant), it possesses some characteristics that are similar to malignant tumors. These include invasion of other tissues with subsequent damage to target organs, resistance to programmed cell death, local and distant metastases, angiogenesis (generation of own blood vessels for tumor maintenance) and responsiveness to hormones of the menstrual cycle. Different types of endometriosis are characterized by distinct biological and clinical features. Disease classification also depends on the anatomic location of the lesion and depth of infiltration. For example, superficial endometriosis usually appears on the surface of the peritoneum or visceral organs, deep infiltrating endometriosis (DIE) typically occurs in the muscle layer of the bladder, rectum, vagina, and diaphragm, while ovarian endometriosis (endometriomas) usually presents as large blood-filled cysts commonly known as “chocolate cysts.” Standard diagnosis  involves clinical examination and imaging (ultrasound, MRI) but the gold standard remains surgery (laparoscopy) and histological examination of the resected tissue to confirm the disease.

Research into the molecular behavior of endometriosis have reported a potential risk for developing epithelial ovarian cancer mainly ovarian clear cell carcinoma (OCCC) and ovarian endometrioid carcinoma (OEC). These forms of ovarian cancers thought to arise predominantly due to endometriosis are collectively referred to as endometriosis-associated ovarian cancers (EAOC). Pathology examination of resected endometriosis tissue enables the identification of patients with hyperplastic (increase in cell production in a tissue or organ) endometriosis who could be at an increased risk of developing EAOC. To differentiate between EAOC and benign cysts, we use the Sampson and Scott diagnostic criteria to establish presence of endometriosis and cancer within the same ovary, to confirm a similar histological structure to that of endometrial tissue, to exclude the possibility of a metastatic tumor affecting the ovary and to show proof of progression from benign endometriosis to a malignant tumor. 

Quantifying cancer risk in women with endometriosis has important public health implications for women in terms of cancer screening and prevention and for clinicians in terms of long term management of women with endometriosis. Epidemiological reports that support an association between endometriosis and EOC estimate that women with endometriosis have two to three times higher risk of developing ovarian cancer and that a high proportion of women with OCCC and OEC also have endometriosis. For instance, a study involving 7911 women with invasive epithelial ovarian cancer in the Ovarian Cancer Association Consortium showed significant association between history of endometriosis and specific histological subtypes of epithelial ovarian cancer including OCCC and OEC. Findings from genetic studies also propose a possible link suggesting that similar genetic factors may increase the risk for both endometriosis and these types of ovarian cancer. Studies that have shed light into disease mechanisms have reported common molecular pathways, including abnormalities in the immune response, inflammation and hormonal regulation, in endometriosis and ovarian cancer that may influence malignant transformation.

Despite advancements in precise diagnostic, prognostic and treatment modalities, data on malignant association between endometriosis and ovarian cancer are still conflicting and there is still no acceptable tool to clinically identify patients at risk of developing endometriosis-associated carcinomas. The relationship between these two diseases warrants in-depth investigation to properly identify the mechanisms and risk factors underlying the transformation of endometriosis to ovarian cancer. This requires a better understanding of the pathophysiology of the disease, histology, genetics, and proteome changes. The development of biomarkers based on molecular alterations identified in endometriosis-associated carcinoma will benefit the clinical evaluation, diagnosis, and management of patients at various stages of malignancy development.

Dr Stella Irungu is a researcher at Integrated Cancer Research Foundation and a Senior Research Scientist at the Kenya Institute of Primate Research (KIPRE).