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AS08. Gynecologic pathology/cytology and disease pathogenesis
PR051/#484  Spatial profiling of ovarian clear cell carcinoma (OCCC) reveals immune-hot features
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  1. Ya-Ting Tai1,
  2. Wei-Chou Lin2,
  3. Duncan Yi-Te Wang3,
  4. Jieru Ye2,
  5. Tuan Zea Tan4,
  6. Lin-Hung Wei5 and
  7. Ruby Yun-Ju Huang3
  1. 1ational Taiwan University, Obstetrics and Gynecology, Taipei, Taiwan
  2. 2National Taiwan University Hospital, Pathology, Taipei, Taiwan
  3. 3National Taiwan University, School of Medicine, Taipei, Taiwan
  4. 4Cancer Science Institute of Singapore, Genomics And Data Analytics Core, Singapore, Singapore
  5. 5National Taiwan University Hospital, Obstetrics and Gynecology, Taipei, Taiwan

Abstract

Introduction OCCC has high incidence in Asia with frequent occurrence at early stage but without sufficient data on molecular stratification for high-risk patients. Recently, immune-hot features have been proposed as an indicator for poor prognosis for early-stage OCCC. Specific patterns of intra-tumoral heterogeneity (ITH) associated with immune-hot features need to be defined.

Methods Formalin-fixed paraffine embedded (FFPE) tumor sections from 10 early-stage OCCC patients were included. Digital Spatial Profiling (DSP) of 18 protein targets was conducted by using the nanoString GeoMx system to profile selected regions of interest (ROIs) based on the reference H&E staining morphology. Areas of illumination (AOIs) were defined according to ROI segmentation by the fluorescence signals of visualization markers pan-cytokeratin (PanCK), CD45, or DNA.

Results Unsupervised hierarchical clustering of 252 AOIs showed 5 distinct clusters. PanCK+ AOIs with ‘immune-like (C1-c)’ (100%) and ‘fibronectin-high (C2-a)’ (45.3%, Chi-square p=2.8E-04) features were associated with OCCC recurrence. Tumor infiltrating immune cells (TIIs) have higher frequencies in PanCK segments with ‘immune signal high (C1-b)’ (45%, Chi-square: p=0.046) and ‘immune-like’ (25%, Chi-square p=0.046) features. Correlating with morphology, tumor samples with recurrence showed higher frequency (54.7%, Chi-Square p =1.01E-04) of papillary pattern. Plus, ROIs with papillary pattern have extremely high frequency (100%) of PanCK segments of ‘immune-like’ feature, higher frequency (65.2%, Chi-Square p=4.99E-04) of TIIs, and macrophage lineage immune mimicry with high intensity of CD68.

Conclusion/Implications Spatial profiling of early-stage OCCC tumors revealed that immune mimicry of tumor cells, the presence of TIIs, and papillary pattern in morphology were associated with recurrence.

Abstract PR051/#484 Figure 1
Abstract PR051/#484 Figure 1
Abstract PR051/#484 Figure 2
Abstract PR051/#484 Figure 2

https://doi.org/10.1136/ijgc-2023-IGCS.92

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