Fallopian Tube Mutation Could Lead to Early Diagnosis of Ovarian Cancer

Screening for cancer cells in the fallopian tubes of high-risk patients may result in early diagnosis of ovarian cancer before it progresses, according to a new study published by Nature Communications.

Previous studies in mice and humans have shown that cancer can start in the fallopian tubes and spread to the ovaries, which is typically when the condition is diagnosed. Currently, it is unknown how and when these cancers develop and how to catch it before it spreads, according to the authors.

In the new study, the authors investigated how cases of high-grade serious ovarian carcinoma (HGSOC) originate from fallopian tube lesions—or p53 signatures—and TP53-mutated serious tubal intraepithelial carcinomas (STICs).

HGSOC is the most common type of ovarian cancer and is typically diagnosed in advanced stages, which is known to result in poor survival and outcomes.

The authors found that the average time from STICs to ovarian cancers was 6.5 years in a 5-patient sample, according to the study. After this period, the cancer quickly metastasized to other areas.

Next-generation sequencing was used to examine 37 samples from STIC lesions, fallopian tube carcinomas, and ovarian cancers. Additional samples were resected from metastases in the appendix, abdomen, and rectum in 3 patients.

The authors also analyzed STIC lesions from 4 patients, 3 of whom had BRCA mutations and underwent procedures to remove their ovaries and fallopian tubes. The fourth patient underwent a hysterectomy and had her ovaries and fallopian tubes removed, according to the study.

The authors discovered that the TP53 gene mutations were observed in all samples, including those in the STIC lesions and other carcinomas. These results suggest that the mutation may be an early predictor of HGSOC, according to the study.

“These data provide much-needed insights into the etiology of ovarian cancer and have important implications for prevention, early detection and therapeutic intervention of the disease,” said researcher Ronny Drapkin, MD, PhD. “It points us to a signature in the tubes to look for, and shows us a window of time to spot these cancers before they morph into something more sinister in the ovaries.”

The investigators then used a mathematical model that could predict the time between the STIC lesions and HGSOC. They found that the time from STICs to ovarian cancer was an average of 6.5 years, but the condition progressed at an average of 2 years among patients with metastatic lesions, according to the study.

The authors said their findings support the current belief that removing the fallopian tubes may reduce the risk of ovarian cancer since it halts the precursors of the disease, according to the study.

The results also highlight new potential approaches for ovarian cancer screening, including advanced mutation detection in liquid biopsies, pap tests, and other fluids.

“These results represent an important step forward that helps fills a knowledge gap on the evolution of this cancer,” Dr Drapkin said. “More studies with a larger cohort of patients are needed to better understand these lesions and the progression into ovarian cancer, but this latest one suggests that examination of the fallopian tubes should become common practice in pathology, and not confined to just academic centers.”