TROP-2 expression in vulval carcinoma – as a possible target for the treatment approach with antibody drug conjugates (ADC)

Question/Background The Trophoblast Cell Surface Antigen 2 (TROP-2) is associated with invasiveness and tumor progression in several malignancies. Strong TROP-2-expression is associated with poor prognosis in cervical carcinoma. Recently, TROP-2 was identified as a target protein for treatment of solid tumors using antibody-drug

conjugates (ADC). There are no details about the expression profiles of TROP-2 in vulval cancer (VCX).

Methods 55 cases of squamous cell carcinomas oft he vulva were

immunohistochemically analysed for TROP-2 expression using a H-score. The staining intensity (SI) was score das negative (0), weak (1), moderate (2) and strong (3). The percentage of positive stained tumor cells was calculated as 0 (complete negative staining of tumor cells), 1 (1-10% positive stained tumor cells), 2 (11-50%) and 3 (51-100%). Overall staining

results were calculated by SI x percentage staining score as follows: negative (core 0), + (scores 1;2;3), ++ (scores 4-6) and +++ (score 7-9) as previously described. Overall staining scores were compared to the molecular subtypes of vulval carcinoma, defining p16+ve/p53wt, p16-ve/p53mut and p16-ve/p53wt VCX. Staining evaluation of TROP-2 was blinded to the molecular subtype.

Results All 55 cases were immunohistochemically positive for TROP2. 7 cases (13%) showed weak reactivity (+), 31 cases (56%) represented moderate reactivity (++) and 17 cases (31%) strong positivity (+++). There were no significant differences within the median h-score values when the different molecular subtypes of vulvar cancer were compared (9 in p16+ve/p53wt versus 6 in p16-ve/p53mut versus 4 in p16-ve/p53wt ; p=0.079).

Conclusion It has been shown that the antibody drug conjugate (ADC) topoisomerase-1-inhibitor irinotecan, coupled via a linker to a humanised IgG-1ntibody hRS7 binding to TROP-2 (i.e. sacitumzumab) represents an effective treatment approach to several carcinoma types. Virtually all examined VCX showed at least weak staining for TROP-2 within the tumor cells. So, TROP-2 may represent a potential target for ADC in vulval cancer. There are no differences of TROP-2 expression within the different molecular subtypes of VCX.

Publication History

Article published online:
21 June 2023