Trop2 expression, p16 expression status, and histologic subtype in carcinoma of the uterine cervix.

Abstract

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.