A Seoul National University Bundang Hospital (SNUBH) team has discovered a protein biomarker that distinguishes molecular types of endometrial cancer.

The uterus has two large categories the cervix, the entrance to the uterus, and the uterine body, where the fetus grows. Endometrial cancer arises from the endometrium, which constitutes the lining of the uterine body.

While the cancer was not common among Korean patients until a few years ago, it has become the most common gynecological cancer since 2019. Unlike cervical cancer, which is easy to diagnose through early regular check-ups, endometrial cancer is hard to detect during regular check-ups.

In most cases, patients suspect the presence of cancer through bleeding symptoms and only receive a final diagnosis after a biopsy. However, as the biopsy method is difficult and painful, it is difficult to receive regularly during a regular checkup. Therefore, if irregular menstruation, excessive menstruation, or abnormal bleeding other than menstruation appears, it is necessary to suspect endometrial cancer and visit a gynecologist.

If bleeding occurs after menopause, it is necessary to check for endometrial cancer.

The Cancer Genome Atlas (TCGA) classifies endometrial cancer into four molecular types -- polymerase epsilon exonuclease (POLE), MSI-H, CN-low, and CN-high. Separating the types of endometrial cancer is important because it affects the treatment plan and prognosis. Identifying the POLE and CN-low types requires sequencing, but there has been a problem in that it takes a lot of time and money to perform them.

Accordingly, the research team, led by Professors Kim Ki-dong of the Department of Obstetrics and Gynecology and Kim Hyo-jin of the Department of Pathology, conducted a study to find biomarkers that could distinguish the two types by protein immunostaining. Professor Park Tae-seong of the Department of Statistics at Seoul National University also participated.

As a result of analyzing 15 POLE and 76 CN-low tissues included in the TCGA data, the research team used four markers -- BMI, cyclinB1, caspase8, XBP1 – to distinguish POLE and CN-low types.

According to the team, BMI was lower than CN-low in the POLE type, and the expression of cyclinB1 was significantly higher in the POLE type, whereas caspase 8 and XBP1 were further decreased.

When the team looked at the expression level by immunostaining samples of patients who underwent endometrial cancer surgery at SNUBH from 2006 to 2013 for the discovered marker, there was no difference in the expression level of cyclin B1 between the POLE and CN-low types. Therefore, it showed the possibility of replacing the sequencing analysis with immunostaining.

“This study is significant because it discovered a protein immunostaining biomarker that distinguishes the POLE and CN-low types of endometrial cancer for the first time in the world,” Professor Kim Ki-dong said. “It is important to identify which molecular type a cancer patient belongs to, as identifying the molecular type of cancer tissue is essential for a treatment approach tailored to the patient.”

Journal of Gynecologic Oncology published the results of the study.