Integrative spatial profiling of protein and chromosomal alterations across normal, precancer, and cancer revealed the presence of aneuploidy in the normal fallopian tube
Aneuploidy is treated as a hallmark of cancer, yet this AACR 2026 poster from Harvard Medical School's Laboratory of Systems Pharmacology uses a single-section ORION-FISH workflow, pairing one-shot Orion multiplexed protein imaging with a 4-plex DNA-FISH assay, to reveal that chromosomal copy-number changes already arise in morphologically normal fallopian tube epithelium along the path to high-grade serous ovarian cancer.
Presented by Harvard Medical School.
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- Aneuploidy was detected in morphologically normal fallopian tube epithelium, not only in invasive cancer. Across a normal-precancer-cancer continuum in high-grade serous ovarian carcinoma (HGSOC), cells carrying extra copies of MYC (8q24) and CCNE1 (19q12) were found in morphologically normal fallopian tube epithelium adjacent to serous tubal intraepithelial carcinoma (STIC) lesions across three incidental STIC cases (n=3), and these cells sat under active immune surveillance.
- A single ORION-FISH workflow reads protein state and chromosomal copy number from the same tissue section. It pairs one-shot Orion multiplexed immunofluorescence (a 16-18-plex antibody panel) with a morphology-preserving 4-plex DNA-FISH assay (MYC/CEP8 and CCNE1/CEP19) on the same FFPE slide, keeping the antigenicity and nuclear morphology that conventional DNA-FISH destroys through protease digestion and permeabilization.
- ORION-FISH copy-number calls matched a clinically approved FISH platform on known-amplified control cases. Validated against clinically approved BioView scoring at 60X (1.42 NA oil objective), ORION-FISH scored extra copies (more than 5 per cell) of MYC in 29% and CCNE1 in 26% of cells in the MYC/CCNE1-amplified HGSOC-1 case, and MYC in 39% and CCNE1 in 9% in the MYC-gain HGSOC-3 case.
