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Updated: Jun 4, 2026
Heterogeneity Mapping of Protein Expression in Tumors using Quantitative Immunofluorescence
Published on: October 25, 2011
Spatial, temporal, and molecular heterogeneity of ADC targets in high-grade serous ovarian carcinoma
Xiaoxuan Li1, Tobias Janik1, Markus Möbs1
1Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Berlin, Germany.
Background:
Antibody-drug conjugates (ADCs) represent a promising therapeutic approach for high-grade serous ovarian carcinoma (HGSOC). Patient selection for ADC therapy depends on tumour target expression, making it essential to characterize molecular, spatial, and temporal heterogeneity.
Methods:
We analyzed two HGSOC tissue microarray cohorts: 100 genomically profiled cases (1565 cores) and 64 matched cases with paired adnexal (A), locally advanced (LA), and recurrent (R) samples (2395 cores). Associations between ADC target expression and molecular characteristics, sampling site, and survival were investigated.
Results:
ADC targets showed no significant associations with homologous recombination deficiency (HRD) or TP53 mutation status; TROP2 was modestly lower in BRCA1/2-mutated tumours. Folate receptor-alpha (FolR1) showed notable spatial heterogeneity: 20.2% switched therapeutic-indication groups between centre and margin at A; 21.7% were reclassified between A and LA. Temporally, all markers showed ≥ 20% switching, reaching 38.4% for FolR1 between A and R. High FolR1 expression in A correlated with poorer survival, a pattern not observed in LA or R samples.
Conclusions:
ADC targets in HGSOC display limited molecular but significant spatial and temporal heterogeneity, with expression classifications varying by site and time. FolR1 expression in adnexal tumours associates with aggressive disease.
Insights
Antibody-drug conjugates (ADCs) for high-grade serous ovarian carcinoma (HGSOC) show varied target expression across tumor sites and over time. Folate receptor-alpha (FolR1) expression in early-stage tumors predicts poorer survival.
Area of Science:
- Oncology
- Translational Research
- Molecular Pathology
Background:
- Antibody-drug conjugates (ADCs) offer a promising treatment strategy for high-grade serous ovarian carcinoma (HGSOC).
- Effective patient selection for ADC therapy relies on accurate assessment of tumor target expression.
- Understanding the heterogeneity of ADC targets is crucial for optimizing treatment efficacy.
Purpose of the Study:
- To investigate the molecular, spatial, and temporal heterogeneity of ADC targets in high-grade serous ovarian carcinoma.
- To assess the association between ADC target expression and key molecular characteristics, sampling site, and patient survival.
Main Methods:
- Analysis of two HGSOC tissue microarray cohorts (100 genomically profiled cases and 64 matched cases with paired adnexal, locally advanced, and recurrent samples).
- Investigation of associations between ADC target expression and homologous recombination deficiency (HRD), TP53 mutation status, BRCA1/2 mutation status, sampling site, and survival outcomes.
Main Results:
- ADC targets showed limited association with HRD or TP53 mutations; TROP2 was lower in BRCA1/2-mutated tumors.
- Significant spatial heterogeneity observed for Folate receptor-alpha (FolR1), with expression classifications changing between tumor sites (e.g., center vs. margin).
- Substantial temporal heterogeneity noted for all markers, particularly FolR1, with expression varying between adnexal, locally advanced, and recurrent disease stages. High FolR1 in adnexal tumors correlated with poorer survival.
Conclusions:
- ADC targets in HGSOC exhibit significant spatial and temporal heterogeneity, impacting expression classification based on sampling site and disease stage.
- FolR1 expression in adnexal HGSOC is associated with more aggressive disease and poorer survival.
- These findings underscore the complexity of ADC target expression in HGSOC and highlight the need for comprehensive characterization to guide patient selection and treatment strategies.
