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Trop2 expression, p16 expression status, and histologic subtype in carcinoma of the uterine cervix
Grit Gesine Ruth Hiller1, Benjamin Wolf2, Mirjam Forberger1
1Division of Gynecologic, Breast and Perinatal Pathology, Institute of Pathology, University Hospital Leipzig, Leipzig, Germany.
Introduction:
The antibody-drug conjugate (ADC) Sacituzumab-Govitecan (SG), a humanized anti-Trop2 monoclonal antibody linked to the cytotoxic topoisomerase I inhibitor SN38, achieved promising results in the treatment of various solid tumors. Treatment approaches with SG requires the expression of Trop2 within tumor cells. The present study explored immunohistochemical Trop2 expression in cervical carcinomas in correlation with histologic subtypes and p16 expression status.
Material And Methods:
Using an immunoreactive score (IRS), immunohistochemical Trop2 expression in surgically treated cervical carcinoma specimens was evaluated by comparing squamous cell carcinomas and adenocarcinomas, and the expression status of p16 as a surrogate marker for high-risk HPV infection.
Results:
A total of 101 cases were included in this study. Of these 75% were squamous cell carcinomas, and 25% were adenocarcinomas, and 5% showed negative immunoexpression for p16, indicating HPV-independent carcinoma. All tumors showed at least weak Trop2 expression. There were no differences in the mean Trop2 IRS-scores comparing histological subtype [squamous: 8.5 (3-9) vs. adeno: 6 (1-9); p = 0.8] and p16 expression status [positive: 9 (6-9) vs. negative: 8 (6-9; p = 0.6]. No differences in Trop2 expression were observed when post-surgical tumor stage, pelvic lymph node status and peritumoral stromal remodelling (desmoplastic response and peritumoral infiltrating lymphocytes) were analysed.
Conclusion:
Regardless of the histologic tumor type and p16 expression status, cervical carcinomas show high Trop2 expression and, therefore, may represent a promising therapeutic target. Clinical trials exploring Trop2 directed ADCs such as Sacituzumab-Govitecan are warranted in this cancer type, including the prognostically poor HPV-independent (p16 negative) tumors, mainly adenocarcinomas.
Significance:
Regardless of the histologic tumor type and p16-expression status, cervical carcinomas show high Trop2 expression, which may therefore represent a promising therapeutic target in these tumors.
Insights
Cervical cancers consistently express Trop2, a target for antibody-drug conjugates like Sacituzumab-Govitecan. This suggests potential for new treatments across all subtypes, including HPV-independent tumors.
Area of Science:
- Oncology
- Immunohistochemistry
- Molecular Pathology
Background:
- Antibody-drug conjugates (ADCs) like Sacituzumab-Govitecan (SG) show promise for solid tumors.
- SG efficacy relies on Trop2 expression in tumor cells.
- Cervical cancer treatment requires understanding Trop2 expression patterns.
Purpose of the Study:
- To investigate Trop2 expression in cervical carcinomas.
- To correlate Trop2 expression with histologic subtypes (squamous cell carcinoma vs. adenocarcinoma).
- To assess Trop2 expression in relation to p16 status (HPV infection marker).
Main Methods:
- Immunohistochemistry was used to evaluate Trop2 expression.
- Immunoreactive scores (IRS) quantified Trop2 levels.
- Specimens from 101 cervical carcinoma cases were analyzed.
Main Results:
- All cervical tumors exhibited at least weak Trop2 expression.
- No significant differences in Trop2 expression were found between squamous cell carcinomas and adenocarcinomas.
- Trop2 expression levels were similar in p16-positive and p16-negative tumors.
Conclusions:
- Cervical carcinomas demonstrate high Trop2 expression irrespective of histologic type or p16 status.
- Trop2 is a viable therapeutic target in cervical cancer.
- Clinical trials of Trop2-targeted ADCs, including for HPV-independent tumors, are warranted.
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