Types of Ovarian Cancer
One of the first major breakthrough discoveries for OVCARE was that ovarian cancer is not a single disease but is made up of several different distinct histotypes. The main histotypes are epithelial in origin and include High-Grade Serous Carcinoma, Clear Cell Carcinoma, Endometrioid Carcinoma, Low-Grade Serous Carcinoma, and Mucinous Carcinoma. There are many other rare types that are non-epithelial in origin.
OVCARE began looking at each of these histotypes separately and soon realized that they differed from one another in many areas such as origin, response to treatment, and aggressiveness. It became apparent that one reason no major breakthroughs had been made in improving ovarian cancer outcomes was because in the past all of these unique histotypes were considered to be a single disease.
OVCARE is now focused on research that develops strategies to specifically target each of these histotypes to improve outcomes for women with ovarian cancer. For more information, visit our Research section.
a) Epithelial origin
High-Grade Serous Carcinoma
High-grade serous carcinoma is the most malignant form of ovarian cancer and accounts for up to 70% of all ovarian cancer cases. The majority of high-grade serous ovarian cancers have recently been found to originate in the fallopian tube, not the ovary. In British Columbia, approximately 25% of women with this form of ovarian cancer have an inherited abnormality in BRCA1/2 genes (note that there is some variation in this figure around the world). Because of their origin in the fallopian tube, serous carcinomas spread through the abdomen very early in the course of disease, and by the time they become symptomatic they are usually high stage tumors, with resulting poor outcomes. OVCARE has developed a promising strategy to tackle this form of ovarian cancer and prevent it before it has the chance to develop.
Clear Cell Carcinoma
Ovarian clear cell carcinoma is the second most common histotype accounting for about 10-13% of women diagnosed with ovarian cancer. This type is often associated with endometriosis, which is the most likely precursor lesion. OVCARE is working on studies that are focused on finding ways to predict whether endometriosis may develop into cancer. Clear cell carinomas are most commonly detected at a low stage in comparison to high-grade serous carcinomas. They do not respond well to the standard platinum/taxane-based ovarian cancer chemotherapy: response rates are 15% compared to 80% for high-grade serous carcinomas. A recent study by the OVCARE team was published on the positive effects of radiation therapy on clear cell carcinoma (but not on high-grade serous carcinoma), giving hope for improved outcomes through type specific treatments.
Endometrioid Carcinoma is the third most common histotype of ovarian cancer and like clear cell carcinoma is believed to arise from endometriosis. This histotype of ovarian cancer is commonly diagnosed at a low stage and is low grade in more than 90% of cases. OVCARE has found that most patients with endometrioid carcinoma, when diagnosed at low-stage, need no additional treatment beyond surgery, allowing these patients to be spared the toxicity of chemotherapy. OVCARE is currently working on research projects that focus on finding similar mutations in atypical endometriosis, the putative precursor lesion, in the hope of eventually finding ways to predict risk of endometriosis progressing to carcinoma.
Mucinous carcinomas account for 4% of ovarian carcinomas and are commonly diagnosed at a low stage. Unfortunately, mucinous carcinomas are known to have a low response rate to chemotherapy. As a result of this knowledge, OVCARE has explored the possibility of specific targeted therapy for this form of ovarian cancer, and identified a subset of mucinous carcinomas that have amplification and over-expression of the HER2 oncogene (which is also amplified and over-expressed in a subset of breast carcinomas); these patients stand to benefit from therapy with targeted therapy.
Low-Grade Serous Carcinoma
Low-grade serous carcinoma is the least common histotype of ovarian cancer, and as such, our knowledge of this ovarian carcinoma type, which was only recently identified, is very limited. Low-grade serous carcinoma is commonly diagnosed at high stage, and these patients have a poor prognosis, even though this tumor is relatively slow growing. OVCARE is currently studying molecular abnormalities in this histotype in the hope of identifying new, more effective treatments.
b) Non-epithelial origin
There are several rare types of non-epithelial ovarian cancers. OVCARE has led a number of unique initiatives recently, and has new projects in place to find better treatment for these diseases. Some of these tumour types include germ cell tumours, stromal tumours such as granulosa cell tumor and Sertoli Leydig cell tumor. OVCARE has published two breakthrough studies in the New England Journal of Medicine on non-epithelial types of ovarian carcinomas. One of these papers focuses on FOXL2 mutations in adult-type granulosa cell tumors and the other study discovered recurrent DICER1 mutations in non-epithelial ovarian cancers. OVCARE has several follow up projects that will build upon these major discoveries. OVCARE is also launching a new clinical approach to improving treatment of rare tumors called SMART (Shared Access Medicine; Approach to Rare Tumours).