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Updated: Jun 28, 2026
Heterogeneity Mapping of Protein Expression in Tumors using Quantitative Immunofluorescence
Published on: October 25, 2011
Human epidermal growth factor receptor-2, nectin-4, and trophoblast cell surface antigen-2 expression varies
Shih-Yao Lin1, San-Chi Chen2, Nai-Ming Cheng3
1Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Objective:
Patients with advanced-stage ovarian cancer (OC) have limited therapeutic options. Antibody-drug conjugates (ADCs) targeting human epidermal growth factor 2 (HER2), nectin-4, and trophoblast cell surface antigen 2 (TROP2) have shown efficacies in various cancers and may benefit patients with OC. The antigen expression may vary across histotypes and affect patient selection but relevant data is variable in OC. This study aimed to evaluate the expression of HER2, nectin-4, and TROP2 in an OC cohort comprising different histotypes with clinicopathological correlation.
Materials And Methods:
Patients diagnosed with high-grade serous carcinoma (HGSC), clear cell carcinoma (CCC), endometrioid carcinoma (EC), or mucinous carcinoma (MC) of the ovary between 2021 and 2023 were retrospectively collected. Demographics and pathological slides were reviewed. HER2, nectin-4, and TROP2 immunohistochemical stains were performed and scored (HER2, ASCO/CAP gastroesophageal adenocarcinoma guidelines; nectin-4 and TROP2: H-score).
Results:
Ninety-two cases were collected, including 33 HGSC, 27 EC, 24 CCC, and eight MC. Three (3.3%) cases showed HER2 positivity (score 3+), significantly more common in MC (25.0%) than in HGSC (0%, P = 0.034) and EC (0%, P = 0.047). Forty-two (45.7%) cases showed weak nectin-4 expression (median H-score: 10), significantly lower in CCC (median H-score: 0) than in HGSC (median H-score: 15, P < 0.001), EC (median H-score: 17, P = 0.001), and MC (median H-score: 17, P = 0.002). Fifty-nine (64.1%) cases showed weak to strong TROP2 expression (median H-score: 30), significantly higher in EC (median H-score: 62) than in HGSC (median H-score: 29, P = 0.026), CCC (median H-score: 8, P < 0.001), and MC (median H-score: 35, P = 0.027), and significantly higher in HGSC than in CCC (P = 0.022).
Conclusions:
HER2, nectin-4, and TROP2 expression showed significant variation across ovarian cancer histotypes.
Insights
This study reveals varying expression of HER2, nectin-4, and TROP2 across ovarian cancer histotypes, crucial for selecting patients for antibody-drug conjugate therapies.
Area of Science:
- Oncology
- Pathology
- Translational Research
Background:
- Advanced-stage ovarian cancer (OC) has limited treatment options.
- Antibody-drug conjugates (ADCs) targeting HER2, nectin-4, and TROP2 show promise in various cancers.
- Antigen expression variability in OC impacts patient selection for targeted therapies.
Purpose of the Study:
- To evaluate HER2, nectin-4, and TROP2 expression in a diverse ovarian cancer cohort.
- To correlate antigen expression with clinicopathological features across different OC histotypes.
Main Methods:
- Retrospective collection of 92 ovarian cancer cases (HGSC, CCC, EC, MC) from 2021-2023.
- Immunohistochemical staining for HER2, nectin-4, and TROP2.
- Scoring using established guidelines (HER2) and H-score (nectin-4, TROP2).
Main Results:
- HER2 positivity (3.3%) was more frequent in mucinous carcinoma (25.0%).
- Nectin-4 expression was significantly lower in clear cell carcinoma (CCC) compared to other histotypes.
- TROP2 expression was highest in endometrioid carcinoma (EC) and HGSC, and lowest in CCC.
Conclusions:
- Significant variations in HER2, nectin-4, and TROP2 expression exist among ovarian cancer histotypes.
- These findings are critical for guiding patient selection for targeted ADC therapies.
- Further research can refine therapeutic strategies based on specific histotype-associated antigen profiles.
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