FALLOPIAN TUBE THE SOURCE OF MOST OVARIAN CANCERS

Mounting evidence suggests that most, if not all, serous ovarian cancers start in the fallopian tubes, not in the ovaries.

Using integrated molecular genomics, researchers confirm and extend prior research showing that high-grade serous carcinomas (HGSCs) in the pelvis are preceded by serous tubal intraepithelial carcinoma (STIC) lesions occurring in the fallopian tubes.

"Based on a better understanding of its origins, our study suggests new strategies for the prevention and early detection of ovarian cancer," senior investigator, Douglas Levine, MD, director, Division of Gynecologic Oncology, Perlmutter Cancer Center at NYU Langone Health in New York City, said in a news release.

The study was published online October 17 in Nature Communications.

For decades it was thought that ovarian cancer originates in the ovarian surface epithelium or cortical inclusion cysts. But recent data suggest that HGSC of the pelvis likely originates from the epithelium of the distal portion of the fallopian tube. STIC lesions, the putative precursor to HGSC, have been found in the fallopian tube and in about half of advanced-stage HGSCs.

To better understand the molecular cause of HGSC, Dr Levine and colleagues analyzed 96 HGSCs, half with a STIC lesion and half without a STIC lesion.

"Usually cancers that begin from different anatomic sites have different genomic profiles," Dr Levine noted in an interview with Medscape Medical News. "What this study showed using multiple integrated approaches is that HGSCs all seem to have similar molecular profiles that cannot be easily distinguished. That suggests that the site of origin is shared and the most common biologic explanation would be in the fallopian tube," he said.

In their analysis, HGSC cases with and without STIC lesions shared the most significant focal DNA somatic copy number alterations.  "We found no differences in the 20,000 genes that we can identify. This leads us to believe that these ovarian cancers all originate in the fallopian tubes," said Dr Levine.

In addition, RNA sequence and microRNA failed to identify any clear separation between cases with and without STIC lesions.  HGSCs had molecular profiles more similar to normal fallopian tube epithelium than to ovarian surface epithelium or peritoneum.

A Practice-Changing Paradigm Shift 

The data support the rationale to focus on the distal fallopian tube when surgical or medical approaches to prevent HGSC are being considered, the researchers say. 

"This whole paradigm shift that ovarian cancers start in the fallopian tubes is already changing practice," Dr Levine told Medscape Medical News. 

He further explained: "We now take out the fallopian tubes when it's convenient to do so. Many patients have their tubes tied for contraceptive purposes, which works. But if you take the tubes out, that also works, and it may help to prevent ovarian cancer. In very select situations — women who are at very high risk for ovarian cancer — our recommendation at the appropriate age is to have the ovaries and fallopian tubes removed."

The findings also have implications for early detection of ovarian tumors. If biomarkers can be found for these tubal cells, future blood tests, advanced Papanicolaou (Pap) smears, or direct tests on tubal tissue might be able to detect ovarian cancer earlier, the researchers say.

"Now that we believe that ovarian cancer comes from the fallopian tubes, the question is, could something like a Pap smear detect DNA mutations or protein fragments? Because the fallopian tubes are connected to the cervix and the vagina, we can get very close to them, and proteins and biomarkers can flow between these structures quite easily," Dr Levine told Medscape Medical News.

Reached for comment, Jamie Bakkum-Gamez, MD, Mayo Clinic, Rochester, Minnesota, said, "This is a very interesting study and as a gynecologic oncologist it definitely makes a lot of sense. This study helps us have a greater understanding that all serous cancers and invasive cancers look very similar whether there is a STIC in the fallopian tube or not."

"We already believe that the tube is where serous ovarian cancers start.  This study is a nice molecular validation of what we think is happening," said Dr Bakkum-Gamez.  Currently, she added, "in a lot of practices, when we are doing a hysterectomy for benign indications and leaving the ovaries, we are taking out the fallopian tubes and that is based on the original histopathology data that shows that at least 50% of serous cancers have some sort of STIC lesion associated with them."

"For practices that aren't doing incidental salpingectomy in average-risk women, this is mounting evidence to help support that procedure," she advised. .

The study had no commercial funding. The authors and Dr Bakkum-Gamez have disclosed no relevant financial relationships. 

Nat Comm. Published online October 17, 2017. Abstract

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