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   197P Computational pathology pipeline enables quantification of intratumor heterogeneity and tumor-infiltrating lymphocyte score

   D.G. Tiezzi, A. Fröhlich, F. Chahud, and 1 more author

   Immuno-Oncology and Technology, Dec 2023

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   Tumor mutation burden, intratumor heterogeneity and the cancer related immune infiltrate are associated with response to target and immune therapies in several cancer types. The aim of this study is to establish a computational pathology (CPath) pipeline for investigating useful histopathological features in hematoxylin and eosin (H&E) whole slide images (WSIs). The pipeline allows for the segmentation and classification of nuclei. As an application, a machine learning approach is used to quantify intratumor heterogeneity (ITH) and tumor-infiltrating lymphocyte (TIL) scores.

   @article{Tiezzi2023,
     title = {197P Computational pathology pipeline enables quantification of intratumor heterogeneity and tumor-infiltrating lymphocyte score},
     volume = {20},
     issn = {2590-0188},
     url = {http://dx.doi.org/10.1016/j.iotech.2023.100656},
     doi = {10.1016/j.iotech.2023.100656},
     journal = {Immuno-Oncology and Technology},
     publisher = {Elsevier BV},
     author = {Tiezzi, D.G. and Fr\"{o}hlich, A. and Chahud, F. and Pagnota, S.},
     year = {2023},
     month = dec,
     pages = {100656},
     dimensions = {true},
   }

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   Integrated genomic and molecular characterization of cervical cancer

   The Cancer Genome Atlas Research Network

   Nature, Jan 2017

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   Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Reported here is an extensive molecular characterization of 228 primary cervical cancers, the largest comprehensive genomic study of cervical cancer to date. We observed striking APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A, and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered novel amplifications in immune targets CD274/PD-L1 and PDCD1LG2/PD-L2, and the BCAR4 lncRNA that has been associated with response to lapatinib. HPV integration was observed in all HPV18-related cases and 76% of HPV16-related cases, and was associated with structural aberrations and increased target gene expression. We identified a unique set of endometrial-like cervical cancers, comprised predominantly of HPV-negative tumors with high frequencies of KRAS, ARID1A, and PTEN mutations. Integrative clustering of 178 samples identified Keratin-low Squamous, Keratin-high Squamous, and Adenocarcinoma-rich subgroups. These molecular analyses reveal new potential therapeutic targets for cervical cancers.

   @article{2017,
     doi = {10.1038/nature21386},
     url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354998/},
     year = {2017},
     month = jan,
     publisher = {Springer Science and Business Media {LLC}},
     volume = {543},
     number = {7645},
     pages = {378--384},
     title = {Integrated genomic and molecular characterization of cervical cancer},
     journal = {Nature},
     author = {Network, The Cancer Genome Atlas Research},
   }