Target Population

Female patients
Newly diagnosed endometrial cancer patietns

Description

The molecular classification proposed by The Cancer Genome Atlas (TCGA) plays a crucial role in the diagnosis and treatment of endometrial cancer. Traditionally, endometrial cancer has been categorized into Type I and Type II based on histopathological features; however, this conventional classification does not fully account for differences in prognosis and therapeutic response. Through comprehensive genomic analysis, TCGA has divided endometrial cancer into four molecular subtypes: POLE ultramutated, microsatellite instability-high (MSI-H), copy-number low (CN low), and copy-number high (CN high) . This molecular classification provides more accurate prognostic information and helps guide personalized treatment strategies. For example, patients with POLE-mutated tumors have an excellent prognosis and may benefit from de-escalated adjuvant therapy. This classification represents a critical first step in genetic testing and is indispensable for precision medicine in endometrial cancer. However, due to limited awareness and understanding of such genomic testing domestically, only a small number of patients currently receive this test, and the associated costs remain relatively high. Therefore, developing a reliable, cost-effective, and time-efficient testing method has become the driving force behind our department’s active research and innovation in this field.

Key Highlights

To determine whether common POLE (DNA polymerase epsilon [ε]) gene mutations are present in tumor specimens from patients with endometrial cancer.
An innovative detection method that utilizes quantitative polymerase chain reaction (qPCR) in combination with novelly designed nucleic acid primers to precisely detect mutation hotspots within the exonuclease domain of the POLE gene.
A POLE exonuclease domain mutation detection kit developed based on this design, which achieves a mutation detection sensitivity as low as 1%. When validated by comparison with next-generation sequencing (NGS) results, the analyses of 11 pathogenic mutation sites demonstrated high concordance.

Service Data

Newly diagnosed endometrial cancer patients admitted to our institution (Taipei Main Hospital and Tamsui Branch) who were preparing to undergo surgery.
After individual explanation by the attending physician, all patients underwent POLE gene mutation testing, except for those who declined participation.
From September 7, 2024, to October 31, 2025, a total of 50 cases were collected; all completed analysis, achieving a 100% implementation rate.

Featured Outcomes

POLE mutation sites analyzed: P286R (c.857C>G), M295R (c.884T>G), S297F (c.890C>T), F367S (c.1100T>C), D368Y (c.1102G>T), V411L (c.1231G>T/C), L424I/V (c.1270C>A/G), P436R (c.1307C>G), M444K (c.1331T>A), A456P (c.1366G>C), and A459F (c.1376C>T).
Detection sensitivity: 1%.

Safety Outcomes

The raw data must be independently reviewed by the operator and a second staff member to prevent data entry errors.
If discrepant results are identified, the corresponding site must be retested.
The report and raw data must be archived together with the analysis date and case information.

Satisfaction

All testing on the patient side was conducted with informed consent, and written informed consent forms were obtained.
The physicians expressed satisfaction with the communication of the test results.
All collected specimens completed this testing, achieving a 100% completion rate.

International Achievements

This testing method is currently under application for a national patent.
The results obtained using this testing method have been published in an international peer-reviewed journal: Gynecol Oncol. 2025 Aug;199:17–26. doi: 10.1016/j.ygyno.2025.06.006. Epub 2025 Jun 13.

Benefits and Impacts

To implement the latest international molecular classification concepts in the clinical management of endometrial cancer.
To tailor the most appropriate treatment strategies according to molecular subtypes, thereby effectively reducing the risks of overtreatment or undertreatment.
For patients with ultramutated tumors and an excellent prognosis, there is potential in the future to reduce the need for postoperative chemotherapy or radiotherapy, thereby decreasing unnecessary side effects and healthcare costs.