Some aggressive ovarian cancers start in the fallopian tubes, not the ovaries

The most aggressive type of ovarian cancer develops from cells that come from the fallopian tubes rather than the ovaries, according to a small study.

The findings confirm growing scientific suspicion around the origins of the disease, and could lead to news ways to prevent and treat it.

There are 5 types of ovarian cancer, of which high-grade serous ovarian carcinoma (HGSOC) accounts for the majority of cases and is also the most aggressive. It is normally diagnosed late, making it difficult to treat.

Until recently it was thought that the disease developed from cells lining the surface of the ovary, but studies have suggested it might start in the fallopian tubes instead.

And for the first time scientists have traced specific genetic faults from the start of the disease through to it spreading.

“Ovarian cancer treatments have not changed much in many decades, and this may be, in part, because we have been studying the wrong tissue of origin for these cancers,” said Professor Victor Velculescu, from the Johns Hopkins Kimmel Cancer Center in the US and who led the latest study.

“If studies in larger groups of women confirm our finding that the fallopian tubes are the site of origin of most ovarian cancer, then this could result in a major change in the way we manage this disease for patients at risk,” he added.

The study, published in the journal Nature Communications, collected a range of tissue samples from 5 women with HGSOC and analysed the genetic makeup of the cells in each sample. 

In total they collected 37 samples, which included:

• tissue samples containing normal cells
• ovarian cancer tissue
• ovarian cancer tissue that had spread
• small cancers found in the fallopian tubes
• serous tubal intraepithelial carcinoma (STIC lesions)

STIC lesions are altered cells on the surface of the fallopian tube that have genetic changes and can be a precursor to cancer developing.

The scientists also collected samples from women who were deemed at high risk of developing ovarian cancer and had their ovaries and fallopian tubes removed. They studied STIC lesions and normal tissue from 4 women, three of whom had a BRCA gene fault, which increases their risk of breast and ovarian cancer.  

The same genetic faults, found on the p53 gene, were found in all of the cancerous and potentially precancerous samples.

Finding these faults across all stages of the disease suggests the errors could be an early step in the development of ovarian cancer.

Professor Iain McNeish, a Cancer Research UK- funded expert in gynaecological cancers said: “What makes this paper interesting is that the researchers have managed to track specific genetic faults from the start of the disease through to it spreading in the same patient. This is no mean feat.”

He said the cells carrying this faulty gene look normal even under a microscope, making early signs of the disease very hard to spot and track. 

“The study confirms that faults in the p53 gene really are the initiating mutation in this disease, and that the most common form of ovarian cancer starts in the fallopian tube in many cases rather than the ovary, and then spreads.”

The researchers suggest that these ovarian cancers develops due to ‘seeding’, where cancer cells from the fallopian tube move to the ovary and then grow to form a tumour.

If larger studies confirm the team’s findings it could lead to ways to spare women most at risk of ovarian cancer from having their ovaries removed. Instead they could just have their fallopian tubes removed. This would stop them experiencing side effects linked to hormone loss that increases their risk of conditions such as heart disease.