ESTRO 2025 - Abstract Book

S4013

Radiobiology - Tumour radiobiology

ESTRO 2025

epithelioids were established by co culturing tumour surrounded by healthy tissue. Epithelioids were grown for 30 60 days, immune-stained (IS) as described in [3] using tissue-specific markers, and imaged by confocal microscopy or, where indicated, sequenced by single-cell RNA sequencing (scRNA-seq). Results: At day 30, IS tumour epithelioids display key features of HNSCC, including sustained proliferative signalling (EdU, Ki67), decreased cell differentiation (KRT4) and abnormal nuclear morphology (DAPI) and cellular architecture (Wheat Germ Agglutinin), as compared to healthy epithelioids. Cancer epithelioids retain the differences observed between healthy and tumour epithelioids, and can be leveraged to study cellular interactions and co-evolutionary responses to RT. At day 60, IS submandibular gland epithelioids harbour proliferating (EdU), progenitor (SOX2), and all major types of specialised cells, specifically acinar (MIST1, AQP5), ductal (KRT18) and myoepithelial (αSMA). This is corroborated by scRNA-seq analysis at day 40. Conclusion: Epithelioids recapitulate key structural and phenotypic features of the tissues in vivo, and can be maintained without passaging for at least 60 days. This makes them a promising tool to monitor the evolution of somatic mutations in HNSCC samples exposed to RT, and to identify RT modalities that can spare salivary glands. This study may provide insights into the genetic determinants underpinning LRR and into therapies that can reduce the incidence of xerostomia, contributing to the improvement of HNSCC patient outcomes.

Keywords: Epithelioids, Somatic evolution, Radiotherapy

References: [1] Rwigema, J.-C. M., Heron, D. E., et al. (2011). American Journal of Clinical Oncology, 34(4), 372–379. [2] Mercadante, V., et al. (2021). Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 39(25), 2825–2843. [3] Herms, A., Fernandez-Antoran, D., Alcolea, M.P. et al. Nat Genet 56 , 2158–2173 (2024). https://doi.org/10.1038/s41588-024-01875-8

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Digital Poster Expression of ERCC5 gene and its correlation with clinical and pathological parameters in Cervical Cancer HIMANSHU MISHRA 1 , RITUSHA MISHRA 1 , GOPESHWAR NARAYAN 2 , LAVINA CHAUBEY 3 , BISHNU PARIDA 2 1 Radiotherapy and Radiation Medicine, IMS, BHU, Varanasi, India. 2 Molecular and Human Genetics, Institute of Science, Varanasi, India. 3 Gynaecology and Obstetrics, IMS, BHU, Varanasi, India Purpose/Objective: Carcinoma Cervix is one of the leading causes of cancer related deaths among females. DNA repair pathways are implicated both in carcinogenesis and progression of cancer. The genetically determined baseline expression level of DNA repair genes are associated with risk of cervical pre-cancer and cancer. The aim of the study was to evaluate expression level of one such DNA repair gene - Excision Repair Cross- Complementation Group 5 (ERCC5) and its correlation to clinical and pathological parameters in cervical cancer. Material/Methods: Expression profiling of ERCC5 gene in 70 histopathologically confirmed cervical cancer biopsies and 35 control (hysterectomy) samples was done using real time PCR(q-PCR), western blot analysis. All patients were planned to be treated by External Beam Radiotherapy (EBRT) with concurrent chemotherapy followed by brachytherapy.Correlation analysis of expression was done with different demographic parameters and overall survival (OS). T- test and One way ANOVA were used to calculate statistical significance using Graphpad PRISM 9. Survival rates were estimated