HER2-Targeted Antibody–Drug Conjugates Display Potent Antitumor Activities in Preclinical Extramammary Paget’s Disease Models: In Vivo and Immunohistochemical Analyses
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Reagents and Antibodies
2.2. EMPD Patient-Derived Xenografts
2.3. Treatment Experiments Using HER2 Inhibitors and HER2-Targeted ADCs
2.4. Histopathological Analyses
2.5. TUNEL Assays
2.6. Patient Selection
2.7. Statistical Analyses
3. Results
3.1. HER-2-Targeted ADCs Regress the Tumor Growth of EMPD-PDXs
3.2. HER2 Expression Correlates with Invasion and Disease-Specific Survival
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviation
ADC | antibody–drug conjugate |
EMPD | extramammary Paget’s disease |
HER2 | human epidermal growth factor receptor 2 |
IHC | immunohistochemistry |
LN | lymph node |
PDX | patient-derived xenograft |
T-DM1 | trastuzumab emtansine |
T-DXd | trastuzumab deruxtecan |
TUNEL | TdT-mediated dUTP nick end labeling |
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Total Number | HER2- Negative | HER2- Positive | p Value | ||
---|---|---|---|---|---|
Cases | 79 | 51 | 28 | ||
Age | Range | 46–94 | |||
(Mean) | −74.59 | ||||
Sex | Male | 44 (55.7%) | 27 | 17 | 0.33 |
Female | 35 (44.3%) | 24 | 11 | ||
Primary site | Genital/anal | 74 | 46 | 28 | 0.17 |
Axillary | 4 | 4 | 0 | ||
Inguinal | 1 | 1 | 0 | ||
Clinical stage | In situ | 34 (43.1%) | 25 | 9 | 0.07 |
I | 5 (6.3%) | 4 | 1 | ||
II | 31 (39.2%) | 18 | 13 | ||
III | 6 (7.6%) | 3 | 3 | ||
IV | 3 (3.8%) | 1 | 2 | ||
EMPD pathology | In situ | 34 (43.1%) | 25 | 9 | 0.006 |
Microinvasive | 16 (20.2%) | 13 | 3 | ||
Invasive | 29 (36.7%) | 13 | 16 | ||
Lymph node metastasis | + | 6 (7.6%) | 3 | 3 | 0.44 |
- | 73 (92.4%) | 48 | 25 | ||
Outcome | Alive | 70 (88.6%) | 49 | 21 | 0.008 |
Dead | 9 (11.4%) | 2 | 7 |
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Tokuchi, K.; Maeda, T.; Kitamura, S.; Yanagi, T.; Ujiie, H. HER2-Targeted Antibody–Drug Conjugates Display Potent Antitumor Activities in Preclinical Extramammary Paget’s Disease Models: In Vivo and Immunohistochemical Analyses. Cancers 2022, 14, 3519. https://doi.org/10.3390/cancers14143519
Tokuchi K, Maeda T, Kitamura S, Yanagi T, Ujiie H. HER2-Targeted Antibody–Drug Conjugates Display Potent Antitumor Activities in Preclinical Extramammary Paget’s Disease Models: In Vivo and Immunohistochemical Analyses. Cancers. 2022; 14(14):3519. https://doi.org/10.3390/cancers14143519
Chicago/Turabian StyleTokuchi, Keiko, Takuya Maeda, Shinya Kitamura, Teruki Yanagi, and Hideyuki Ujiie. 2022. "HER2-Targeted Antibody–Drug Conjugates Display Potent Antitumor Activities in Preclinical Extramammary Paget’s Disease Models: In Vivo and Immunohistochemical Analyses" Cancers 14, no. 14: 3519. https://doi.org/10.3390/cancers14143519