Researchers at MUSC Hollings Cancer Center have uncovered new evidence while developing a new model for ovarian cancer, suggesting that serous uterine cancer may actually originate in the fallopian tubes rather than the uterus. This indicates that the cancer could already be metastatic when detected within the uterus.
Most uterine cancers have impressive five-year survival rates, reaching as high as 95% for localized cases. However, serous uterine cancer is a notable exception, with survival rates between 35% to 50% in the first two stages.
The team’s new findings were detailed in a paper published this month in Cancer Research Communications. The senior author, Joe Delaney, Ph.D., credited this discovery to a fundamental aspect of science—curiosity.
While the team was creating a much-needed model of ovarian cancer, they were pleased to see expected cancer signals in the fallopian tubes and ovaries but were surprised to find them in the uterus as well.
Delaney remarked, “We noticed unexpected signals in the uterine epithelial cells that shouldn’t exhibit these cancer markers, given that this driver is only expressed in the fallopian tubes.”
They anticipated finding cancer signals in the fallopian tubes since they had specifically targeted that area with an oncogene, which is a gene that facilitates cancer growth. Delaney explained why they focused on the fallopian tubes: “About 80% of ovarian cancers actually start there, not in the ovaries.”
His pursuit of a new ovarian cancer model stemmed from the absence of one relevant to most ovarian cancer patients. While some models exist, they are tailored for cases caused by mutations in the PTEN or BRCA genes, which only account for a small percentage of ovarian cancers.
“This leaves around 75% of patients without a suitable genetic model,” Delaney added. Such models are crucial for understanding cancer’s mechanisms and for the development and testing of new therapies.
Seven years ago, his team embarked on creating a new ovarian cancer model not based on the removal of tumor suppressors but on the MYC oncogene, which is linked to the growth of around 70% of human cancers. Previously unused in ovarian cancer research, they directed this oncogene specifically towards the fallopian tubes.
The outcome resulted in cancer development in both the ovaries and the uterus.
The researchers then cultured these cancer lines in the lab to analyze their similarity to known human cancers. As expected, the ovarian cancer cells resembled human high-grade serous ovarian cancer. However, they were surprised to find that the uterine cancer cells also shared similar traits. “The uterine cancer cells appeared transcriptionally alike to the high-grade serous ovarian cancer cells,” Delaney noted.
Curious about these findings, Delaney conducted a literature search and found previous studies that aligned with his observations.
For instance, a study from McMaster University in Canada analyzed samples from various gynecological cancers without prior diagnosis knowledge. They identified serous tubal intraepithelial carcinoma (STIC), a precancerous condition, in cases of uterine and serous ovarian carcinoma, but not in forms of non-serous uterine cancer or benign conditions.
“The rates of STIC lesions were identical in uterine serous carcinoma and high-grade serous ovarian cancer patients,” Delaney explained.
Another study from Sweden reviewed uterine cancer rates over 37 years, comparing women who underwent tubal ligation— a surgical procedure that blocks fallopian tubes— to those who did not. The results indicated that tubal ligation may lower the incidence of uterine cancer, particularly the aggressive type, by preventing cancer cells from migrating from the fallopian tube to the uterus.
Delaney remarked, “Those researchers could only speculate since they lack a lab, but we aim to test these findings through a mouse model, observing the rates of serous uterine cancer after removing fallopian tubes.”
“We anticipate results in approximately two years,” he stated.
In the meantime, other researchers have expressed interest in utilizing this new model. It holds the potential for studying how high-grade serous ovarian cancer develops in women without gene mutations and for investigating treatment options.
Moreover, this model could serve as a platform for researching uterine serous carcinoma as well.
“We may have inadvertently created the first mouse model that closely resembles uterine serous carcinoma,” Delaney noted. “What we’re identifying as uterine cancer might actually be a metastatic ovarian cancer, and we have been mislabeling it all along.”
Delaney described the unexpected discovery as exhilarating, stating, “I was examining these slides with my trainees, and I shared in their excitement fully.”
