Scientists at The University of Texas have identified genetic mutations in endometrioid endometrial carcinoma (EEC), the most common form of this cancer of the uterine lining. The mutations revealed a more lethal version of an EEC subtype previously thought to respond well to treatment. It’s possible that by identifying these patients early on, oncologists can try more aggressive treatment approaches to increase the likelihood for a positive outcome.

With endometrial cancer, the most common gynecological cancer in the western world and the fourth most prevalent in the U.S., it can literally be a matter of life and death. Mortality rates from this cancer have nearly tripled in the last 25 years and are thought to be attributed to the rising incidence of obesity.

EEC is categorized into subtypes that help determine risk of recurrence and guide treatment.  Most patients have Type I, which can be diagnosed early and generally has a good outcome with treatment.  Type I accounts for 70 to 80 percent of all EECs. Type II is more troublesome and is usually diagnosed late in the cancer’s progression resulting in a poor prognosis. The team, however, identified a cluster of patients within Type I that appears to have a more virulent form of it previously not recognized. The researchers labelled this patient group as Cluster II.

The patients were mostly younger and obese that’s typical for Type I. What’s unusual is for patients in this disease category to have decreased survival rates.  Molecular subtyping of EEC may help oncologists with diagnosis and prognosis within this unique subset.

The team believes that by being able to identify molecular attributes, physicians can identify EEC patients at risk for this more lethal form of the disease.

The team discovered distinctive genetic mutations in 87 percent of the Cluster II 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.

With the identification of Cluster I (young, obese patients who respond well to treatment and generally have a good prognosis) and the more lethal Cluster II, the researchers demonstrated that, like twins, the two cancers may appear similar, but they have distinct genetic differences that make them unique. In the case of Cluster II, the discovery of these chromosomal quirks could lead to earlier and more effective treatments.

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.  Endometrial cancer in this patient population is much more complex than the medical community were previously led to believe.

The team hope that the study results can help pave the way for more precision-based, individualized therapy of endometrial cancer patients who have tumours with CTNNB1 mutations.

Source:  The University of Texas MD Anderson Cancer Center