J Gynecol Oncol.  2025 Jan;36(1):e14. 10.3802/jgo.2025.36.e14.

HER2-negative or low expression as an unfavorable prognostic factor in patients with stage I/II uterine carcinosarcoma

• Mizoguchi C
• Nishikawa T
• Yoshida H
• Yasuda M
• Kato T
• Hasegawa K
• Yonemori K

• KMID: 2565442
• DOI: http://doi.org/10.3802/jgo.2025.36.e14

Abstract

Objective
Uterine carcinosarcoma (UCS) is uncommon high-grade endometrial cancer with limited treatment options. We evaluated the prognostic significance of human epidermal growth factor receptor 2 (HER2) expression and HER2 gene amplification within large cohorts of UCS, and clarify clinicopathologic characteristics of HER2-low UCS.
Methods
We examined HER2 protein expression in 148 patients of UCS using in vivo diagnostic HER2 immunohistochemistry (IHC) kits and HER2 gene amplification using fluorescence in situ hybridization (FISH) in 72 patients.
Results
HER2 IHC score was evaluated according to the latest American Society of Clinical Oncology/College of American Pathologists criteria for gastric cancer, which was negative in 41 patients, low expression of 1+ was observed in 57 patients, and HER2 high expression was observed in 50 patients (2+ in 38 and 3+ in 12 patients). There was no significant statistical difference in clinicopathological characteristics based on HER2 protein expression status. HER2 negative and low expression compared to high expression revealed poor overall survival in stage I/ II. The concordance between IHC and FISH results were relatively low compared to other cancer types (HER2 IHC score 1+, 2+, and 3+ were 5%, 15%, and 50%), and combining these results was not efficient as a prognostic factor in UCS. In contrast, the HER2 IHC score alone was a prognostic factor in stage I/II UCS. HER2 low group did not show specific clinicopathologic features.
Conclusion
Since the HER2 IHC score low in advanced UCS is a predictive factor, stratification of UCS using HER2 IHC score for HER2 IHC score low group and developing adjuvant therapy may be proposed in the near future.

Keyword

Carcinosarcoma; ERBB2 Protein, Human; Immunohistochemistry; In Situ Hybridization; Prognosis