Expression und prognostische Aussagekraft von TROP2, FOLR1 und HER2 in Ovarialkarzinomen
Loading...
Files
Date
relationships.isAuthorOf
Publisher
Philipps-Universität Marburg
item.page.supervisor-of-thesis
Abstract
Approximately 3% of all malignant neoplasms in women are localised in the ovaries. Histologically, these are mostly ovarian carcinomas, which have the highest mortality rate of all gynaecological tumours and are among the most aggressive malignant neoplasms of all. Despite considerable therapeutic progress in the last years, there is a lack of effective treatment strategies, particularly for recurrent, platinum-resistant ovarian carcinomas. Drugs directed against specific tumour antigens (e.g. HER2, TROP2 and FOLR1) are increasingly being used. Against this clinical background, this thesis deals is about the expression of the three proteins mentioned in ovarian carcinomas. Immunohistochemical staining will be used to clarify how the expression of HER2, TROP2 and FOLR1 is distributed within the overall cohort and in subgroups. Furthermore, it is to be evaluated if there are significant correlations between subgroups and protein expression and to what extent the markers have prognostic significance. In addition, the relationship between HRD/BRCA status and the expression of TROP2 and FOLR1 will be analysed.
The analysed cohort of 227 patients consisted predominantly of serous high-grade carcinomas (82%) in advanced stage (64% FIGO III/ IV). TROP2 showed a positive staining reaction in 84% of the tumours and was significantly more frequently expressed by HGSC compared to other histological subtypes (p=0.015). 35% of all tumours expressed FOLR1 and again, a significant accumulation of FOLR1-positive carcinomas was observed among HGSC (p=0.003) and a positive status correlated with pT3 stage (p=0.026). According to the PS2+ scoring method, however, only 14% (low), 11% (medium) and 4% (high) fulfilled the positive criteria. A positive correlation was also found between FOLR1 and TROP2 positivity, although the effect size here was very weak (r=0.174). The following results were obtained in the evaluation of HER2: 3% SIS3+, 1% SIS2+, 5% SIS1+, 3% ultralow, 88% no specific staining pattern. Correlations with subgroups, TROP2 or FOLR1 could not be detected. In univariate survival analyses, TROP2-positive high-grade carcinomas (HR=0.605, p=0.019) and non-HGSC (HR=0.318, p=0.012) showed better survival rates. The expression of FOLR1 did not result in statistically significant differences in overall survival, regardless of the cut-offs used. HER2-expressing HGSC and the group of high-grade carcinomas showed poorer overall survival compared to HER2-negative tumours, both using the cut-off ≥ultralow (HGSC: HR=1.76, p=0.022; HGC: HR=1.87, p=0.008) and ≥1+ (HGSC: HR=1.87, p=0.02; HGC: HR=1.99, p=0.008). In addition, TROP2 in non-HGSC and HER2 in HGSC (cut-off ≥ultralow) proved to be a positive (TROP2: HR=0.112, p=0.022) or negative (HER2: HR=1.98, p=0.028) prognostic parameter, even when other relevant prognostic factors (pN, pT and R status) were taken into account. A correlation between the expression of TROP2 or FOLR1 and HRD/BRCA status could not be proven.
From an epidemiological perspective (age and stage at first diagnosis, distribution and prognosis of histological subtypes), the results of this study are largely consistent with the data published for ovarian cancer. Furthermore, the prognostic relevance of established parameters (pT, pN, R, FIGO) was confirmed. The expression of TROP2, FOLR1 and HER2 has already been demonstrated at protein level in several studies. However, the percentage of FOLR1- and HER2-positive carcinomas in our cohort was in the lower range of published results. In contrast to comparable publications, TROP2 expression was associated with better survival rates in the present study. In line with other published data, FOLR1, on the other hand, showed no significant correlation between expression and overall survival. The negative prognostic significance of HER2 from this study is also consistent with numerous publications on this topic. Studies regarding the correlation between TROP2 or FOLR1 expression and HRD or BRCA status have not yet been published. Limiting factors of the present study are the retrospective composition of the cohort as well as a heterogeneous regimen for tumour treatment, the use of different antibodies and cut-offs for categorisation and the composition of the cohort itself, which impair the comparability with other authors.
Apart from the prognostic value and tumour-biological properties of the biomarkers, their expression in carcinomas appears to be far more important from a therapeutic point of view, as they represent target structures of modern oncological treatment methods. For example, the antibody-drug conjugate mirvetuximab-soravtansine directed against FOLR1 has already been approved for ovarian carcinomas, provided that immunohistochemical expression has been proven. Other ADCs against TROP2 (e.g. sacituzumab govitecan) and HER2 (e.g. trastuzumab deruxtecan) are currently undergoing clinical trials.
Review
Metadata
Contributors
Supervisor:
Dates
Created: 2025Issued: 2025-08-11Updated: 2025-08-11
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
ovarian cancer
DFG-subjects
TROP2FOLR1OvarialkarzinomHER2
DDC-Numbers
610
show more
Gleitsmann, Moritz: Expression und prognostische Aussagekraft von TROP2, FOLR1 und HER2 in Ovarialkarzinomen. : Philipps-Universität Marburg 2025-08-11. DOI: https://doi.org/10.17192/z2025.0418.