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Strategy for Biobanking of Ovarian Cancer Organoids: Addressing the Interpatient Heterogeneity across Histological Subtypes and Disease Stages
Published on: February 23, 2024
Immunohistochemical and molecular diagnostics tailoring personalised ovarian cancer therapy
Adam Michał Kowalewski1,2, Łukasz Szylberg1,3
1Department of Tumour Pathology, Oncology Centre, Prof. Franciszek Lukaszczyk Memorial Hospital, Bydgoszcz, Poland.
Abstract:
Ovarian cancer remains the most lethal gynaecological malignancy, and it exhibits substantial histologic and molecular heterogeneity. Traditional systemic therapies have produced only modest survival gains. Integration of immunohistochemical (IHC) and molecular diagnostics has shifted care toward biomarker-driven personalised treatment. This review presents current IHC approaches for histotype classification and the most important actionable protein markers (FR, HER2, TROP2, MMR proteins, and PD-L1), together with molecular testing for BRCA1/2, homologous recombination deficiency (HRD) status, and circulating tumour DNA (ctDNA) monitoring. These diagnostics now direct poly(ADP-ribose) polymerase inhibitors maintenance in HRD-positive disease and antibody-drug conjugates such as mirvetuximab soravtansine in FR-high platinum-resistant tumours. However, important limitations remain: intratumoral heterogeneity, variable assay performance, lack of standardisation, and unequal access to testing worldwide. We also discuss how best to combine multiple biomarkers and outline future directions, such as AI-assisted digital pathology, composite predictive models, and ctDNA-guided adaptive strategies, to refine patient selection and improve long-term outcomes.
Insights
Biomarker-driven diagnostics, including immunohistochemistry and molecular testing, are revolutionizing ovarian cancer treatment by personalizing care. Future strategies aim to combine multiple biomarkers for improved patient selection and outcomes.
Area of Science:
- Oncology
- Gynaecological Pathology
- Molecular Diagnostics
Background:
- Ovarian cancer is a highly lethal gynaecological malignancy with significant heterogeneity.
- Traditional therapies offer limited survival benefits.
- Biomarker-driven approaches are transforming treatment paradigms.
Purpose of the Study:
- To review current immunohistochemical (IHC) and molecular diagnostic strategies for ovarian cancer.
- To highlight key actionable biomarkers and their clinical applications.
- To discuss limitations and future directions in ovarian cancer diagnostics.
Main Methods:
- Review of current immunohistochemical (IHC) techniques for histotype classification.
- Analysis of actionable protein markers (e.g., FRα, HER2, TROP2, MMR proteins, PD-L1).
- Evaluation of molecular testing including BRCA1/2, homologous recombination deficiency (HRD), and circulating tumor DNA (ctDNA).
Main Results:
- Diagnostics guide maintenance therapy with PARP inhibitors in HRD-positive disease.
- Antibody-drug conjugates like mirvetuximab soravtansine are used in FRα-high platinum-resistant tumors.
- Limitations include heterogeneity, assay variability, lack of standardization, and unequal access.
Conclusions:
- Integration of IHC and molecular diagnostics enables personalized ovarian cancer treatment.
- Future directions involve AI-assisted pathology, composite models, and ctDNA-guided strategies.
- Refining patient selection through advanced diagnostics is crucial for improving long-term outcomes.
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