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HER2 expression patterns in paired primary and metastatic endometrial cancer lesions
Mari Kyllesø Halle1,2, Ingvild Løberg Tangen1,2, Hege Fredriksen Berg1,2
1Department of Obstetrics and Gynaecology, Haukeland University Hospital, Jonas Lies vei 72, Bergen 5053, Norway.
Background:
Despite successful implementation of drugs targeting the human epidermal growth factor receptor 2 (HER2) receptor in breast and gastric cancers, the potential of HER2 as a therapeutic target in other cancers has been less studied, including endometrial cancer. We investigated expression levels of HER2 (ERBB2) in a large cohort of endometrial cancer lesions, also including complex atypical hyperplasia and metastatic lesions.
Methods:
67 precursor lesions, 790 primary endometrial cancers and 383 metastatic lesions were investigated for HER2 expression in relation to clinicopathologic features and outcome. Protein levels were assessed by immunohistochemistry (using the HercepTest and staining index (SI) criteria), mRNA levels by microarrays and amplification status by chromogenic in situ hybridisation.
Results:
High HER2 protein levels were significantly associated with features of aggressive disease and increased mRNA ERBB2 levels. HER2 expression defined by the SI proved to be a better predictor of survival compared with the HercepTest. A discordant HER2 expression pattern between paired primary and metastatic lesions was detected, revealing substantial reduction in HER2 expression from primary to metastatic disease.
Conclusions:
Loss of HER2 expression is common in metastatic endometrial cancer lesions and assessment of HER2 levels in the metastatic lesions may be important to define the potential benefit of anti-HER2 treatments in endometrial cancer patients.
Insights
Human epidermal growth factor receptor 2 (HER2) is a potential therapeutic target in endometrial cancer. While high HER2 levels correlate with aggressive disease, expression often decreases in metastatic lesions, impacting treatment decisions.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Human epidermal growth factor receptor 2 (HER2) is a validated therapeutic target in breast and gastric cancers.
- Its potential as a therapeutic target in endometrial cancer remains underexplored.
- This study investigates HER2 expression in endometrial cancer, including precursor and metastatic lesions.
Purpose of the Study:
- To investigate the expression levels of HER2 (ERBB2) in a large cohort of endometrial cancer lesions.
- To correlate HER2 expression with clinicopathologic features and patient outcomes.
- To assess HER2 expression in primary versus metastatic endometrial cancer lesions.
Main Methods:
- Analysis of HER2 protein levels via immunohistochemistry (HercepTest and staining index criteria).
- Assessment of HER2 mRNA levels using microarrays.
- Determination of HER2 amplification status through chromogenic in situ hybridization.
- Investigation of 67 precursor lesions, 790 primary endometrial cancers, and 383 metastatic lesions.
Main Results:
- High HER2 protein levels were significantly associated with aggressive disease features and elevated ERBB2 mRNA levels.
- The staining index (SI) for HER2 expression was a superior predictor of survival compared to the HercepTest.
- A notable discordance in HER2 expression was observed between paired primary and metastatic lesions, with a substantial reduction in metastatic sites.
Conclusions:
- Loss of HER2 expression is frequently observed in metastatic endometrial cancer.
- Assessing HER2 levels in metastatic lesions is crucial for determining the potential benefit of anti-HER2 therapies.
- Findings suggest a need for re-evaluation of HER2 status in metastatic endometrial cancer for personalized treatment strategies.
