British journal of cancer · 2026
Spatial, temporal, and molecular heterogeneity of ADC targets in high-grade serous ovarian carcinoma.
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Li Xiaoxuan, Janik Tobias, Möbs Markus, Florian Stefan, Schmitt Wolfgang D, Dzakulic Amra, Sehouli Jalid, Horst David, Dubois Frank P B, Braicu Elena Ioana, Dragomir Mihnea P
Аннотация
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.
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.