New study aims to determine origin of ovarian cancer

Ovarian cancer only accounts for about 1.3 percent of new cancer cases each year, but less than half of patients survive for five years after diagnosis, according to SEER data from the National Cancer Institute. These poor outcomes are due in part to the fact that ovarian cancer is often diagnosed in late stages after it has already metastasized, or spread to other organs.

For many years, scientists believed that ovarian cancer originates in the ovaries, but research in the past 15 years suggests that it may develop in the fallopian tubes.

"Researchers and clinicians began to investigate the role of the fallopian tube due to the fact that ovarian cancer more closely resembles the cells in the fallopian tube rather than the ovary," said Ernst Lengyel, MD, PhD, Arthur L. and Lee G. Herbst Professor of Obstetrics and Gynecology.

In a recent study published in the journal Cancer Discovery, Lengyel and colleagues aimed to determine the points of origin and eventual metastatic trajectory of high-grade serous ovarian cancer (HGSOC), the most aggressive and deadly type of the disease. The research team also included Samuel Volchenboum, MD, PhD, associate professor of pediatrics, and S. Diane Yamada, MD, Joseph Bolivar DeLee Professor of Obstetrics and Gynecology.

Lengyel and his team recruited eight patients, who had recently been diagnosed with advanced, metastatic HGSOC. The researchers used sequencing technologies to examine genetic mutations in serous tubal intraepithelial carcinomas (STIC), ovarian, fallopian tube, and abdominal tumors in each patient.

STIC are lesions in the fallopian tubes that were identified by researchers as being possible precursors to primary fallopian tube cancers. However, the relationship between STIC and metastatic HGSOC remains unclear.

"By carefully examining which mutations are found in different sites, we can reconstruct how these tumors are connected to one other and which ones are the 'parents' for other sites," Lengyel said.

Previous studies only looked at STIC lesions in the fallopian tubes of patients with BRCA mutations, who have an increased risk for breast and ovarian cancer, whereas none of the patients in Lengyel's study are BRCA carriers. Women with BRCA mutations often choose to have both the fallopian tubes and ovaries removed, a procedure known as prophylactic bilateral salpingo-oophorectomy. In some cases, physicians can detect evidence of early-stage disease in the fallopian tubes after removal.

Lengyel's team, including Mark Eckert, PhD, a postdoctoral scientist in the laboratory, found that STIC lesions in the fallopian tubes do not necessarily mean the cancer is isolated to that location. While the study found that STIC were precursor lesions in half of the patient cohort, in 25 percent of the patients those lesions were actually metastases, meaning the cancer had spread from another location in the abdomen. Further analyses using an innovative tissue culture model revealed that HGSOC tumor cells can implant in the fallopian tubes and mimic STIC lesions.

This finding could impact treatment protocols, especially for BRCA patients who elect to only have fallopian tubes removed because of the current paradigm that the fallopian tubes are the origin of ovarian cancer. "Should we assume that the patient has been cured by the complete removal of a precancerous lesion?" said Lengyel. "Or could this site rather represent a metastasis from a cancer located elsewhere in the abdomen?" Conversely, removing both the fallopian tubes and ovaries might not be necessary in BRCA patients where the precursor lesions are only present in one fallopian tube. This study suggests that the origin of gynecologic cancers isn't always straight forward, and may differ from patient to patient.