Exploring the molecular landscape of ovarian cancer through immunohistochemistry multi-marker prevalence screening

Ovarian cancer (OVCA), and particularly its most aggressive form, highgrade serous ovarian cancer (HGSOC), presents a major challenge to women's health worldwide. Standard treatments include cytoreductive surgery and platinumbased chemotherapy, which can achieve initial improvement but impose substantial physiological strain and are often followed by relapse. Despite the application of newer modalities such as antiangiogenic therapies and PARP inhibitors, longterm positive outcomes remain limited for many patients. As such, the market is being reshaped by targeted molecular therapies. Understanding the expression levels of key biomarkers in human ovarian cancer tissues is important for the development of next-generation antibody-drug conjugates (ADCs) for cancer treatment. Discovery Life Sciences is a leading CAP/CLIA-certified, ISO-accredited provider of immunohistochemistry (IHC) testing services using formalinfixed, paraffinembedded (FFPE) human tumor samples. To explore the molecular landscape of ovarian cancer, Discovery conducted a multi-marker prevalence screen across serial sections of ovarian cancer samples from an onsite tissue bank using newly developed or established IHC assays for commercial staining platforms. Expression of MUC16, NaPi2b, B7-H4, TROP2, MSLN, CDH6, TF, CLDN6, and HER2 was assessed against FOLR1 coexpression. FOLR1 is frequently overexpressed in ovarian cancer and is therefore a clinically meaningful target. For each ovarian cancer sample and biomarker in the screen, IHC staining in tumor cells was evaluated semi-quantitatively by a board-certified pathologist using the H-Score approach [sum of percentages (0-100%) of reactive tumor cells multiplied by their corresponding intensity (0, 1+, 2+, 3+) on a 0-300 scale]. To evaluate the prevalence data, average H-Scores across all samples (n=50) were calculated and graphed for comparison among the 10 biomarkers. Graphs were also generated to display the distribution and relationship between each biomarker and FOLR1 expression in each individual ovarian cancer sample. Multi-marker IHC screening efficiently generates high volume prevalence data to inform biomarker expression for potential selection in the context of ADC therapeutics. Such robust IHC testing is also scalable by biomarkers, sample numbers, and disease indications. In this way, IHC experimentation performed by Discovery Life Sciences supports research and clinical trial applications to customize patient care through advancements in precision oncology.