Origins of Ovarian Cancer

Scientists know that in order to understand how best to defeat a cancer, you need to track how it morphs from a normal cell into a precursor lesion and then develops into a full-blown cancer. Such scientific sleuthing has led to life-saving advances in breast and colon cancers, among others.

But in the case of ovarian cancer, no one had found much evidence of its formative stages on ovaries. That’s because researchers may have been looking in the wrong place.

Evidence is mounting that the fallopian tubes—especially the tendrils that extend like fingers over the ovaries—are likely the origin of many high-grade serous ovarian tumors, a common and aggressive form. Whereas eggs from the ovary move in one direction into the fallopian tubes to the uterus, cancerous lesions from the ends of the tubes apparently move in the opposite direction. They are shed into the ovary, where they grow in the hormone-rich and fertile environment.

Researchers at the Dana-Farber Cancer Institute in Boston have, in a series of studies starting in 2005, discovered that the secretory cells lining the fingerlike projections at the ends of fallopian tubes harbor early serous cancers, and showed that these early cancers had the same genetic mutations as tumors found elsewhere in the pelvis, such as on the ovaries. These scientists learned that the mutated p53 genetic signature they had discovered in these early fallopian tube lesions was also present in normal-looking tubular tissue.

According to Christopher Crum, MD, director of women’s and perinatal pathology at Dana-Farber/Brigham and Women’s Cancer Center, this was an “Aha!” moment that provided both a marker for serous cancers and a developmental pathway.

Other researchers have recently confirmed these findings. Oncologists have found lesions in fallopian tubes of women diagnosed with advanced ovarian cancer, and others have found that cancer can develop in the reproductive tract or other parts of the abdominal cavity of high-risk women who have had their ovaries removed prophylactically.

Does it matter where the tumors originated? Yes, because now these lesions can be studied for genetic markers that may aid in early detection as well as in the development of targeted therapies. And if ovarian cancer originates in the fallopian tubes, then women at risk might consider having their tubes removed and not their ovaries, which would spare them from early menopause. This makes sense because many studies have shown that women who have a tubal ligation (where the tubes are tied) have a substantially lower risk of developing ovarian cancer. However, this information is too premature to affect the current standard of surgery for the treatment or prevention of ovarian cancer.

Some physicians now want to incorporate removal of fallopian tubes when a hysterectomy or tubal ligation is performed. In 2010, gynecological oncologists in British Columbia began a campaign to routinely remove the fallopian tubes to prevent cancer in women, regardless of their ovarian risk profile, who are undergoing those procedures. They say their research shows deaths from ovarian cancer could fall as much as 50 percent if this occurred.