Discovering a more aggressive form of endometrial cancer

Parents of twins often tell them apart through subtle differences such as facial expression, moles, voice tone and gait. Similarly, physicians treating women with endometrial cancer, or cancer of the uterine lining, must be able to distinguish between different versions of this disease that on the surface may appear the same.

“The most common form of endometrial cancer, known as endometrioid endometrial carcinoma, or EEC, is categorized into subtypes that help determine risk of recurrence and guide treatment,” said Wei Zhang, Ph.D., professor of Pathology at MD Anderson.

Seventy to 80% of patients have Type I, which can be diagnosed early and generally has a good outcome with treatment.

However, Zhang identified a cluster of patients within Type I who appear to have a more virulent form of the disease previously not recognized. To differentiate between the two groups, he named the patients with less aggressive Type I cancer “Cluster I,” and the patients with more aggressive Type I cancer “Cluster II.”

On the surface, the Cluster I and Cluster II patients had the same characteristics — they were mostly young and obese, which is typical of Type 1 endometrial cancer. Mortality rates from this cancer have nearly tripled in the last 25 years and are thought to be related to obesity.

But when Zhang and his team began analyzing Cluster II patients’ tumors, they found distinctive genetic mutations in 87% of the patients. The mutations occurred in the CTNNB1 gene, which is necessary for the creation and maintenance of tissue-producing epithelial cells. Within CTNNB1, genetic sequences known as exon 3 created a “hotspot,” a cellular cauldron of biological blunders. This resulted in the normally passive Type 1 becoming deadly for some patients.

“The identification of this second cluster of patients with endometrial cancer helps to refute long-standing teachings that young, obese patients universally have endometrial cancers that are estrogen-driven and thus have a good prognosis,” said Russell Broaddus, M.D., Ph.D., professor of Pathology at MD Anderson. “Endometrial cancer in this patient population is much more complex than we were previously led to believe. ”

Zhang believes that Cluster II patients, if identified early, can be treated more aggressively for a better outcome.

The study’s findings were published in an article appearing in this month’s issue of the Journal of the National Cancer Institute.