A Precursor Lesion in the Fallopian Tube

Multimodal spatial profiling of fallopian tube precursors (Kader et al., 2025), published in Cancer Discovery, asks what changes in the fallopian tube as precancerous lesions progress to high-grade serous ovarian cancer (HGSOC), which arises there. The authors combined highly multiplexed imaging with spatial transcriptomics across stages of the disease: p53 signatures, serous tubal intraepithelial carcinomas (STICs) and invasive cancer.

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Key Findings

• Precursors already show cancer-like changes. The precursor epithelium carries chromosomal instability and persistent interferon signaling.
• MHC class I is raised early. Fallopian tube precursors express more MHC class I, including HLA-E, and more interferon-stimulated genes, changes usually linked to later-stage tumors.
• Immunity shifts from surveillance to suppression. The surrounding immune environment moves from immune surveillance in early STICs to immune suppression in advanced STICs and cancer.

This Slide

The view below is one tissue section imaged by cyclic immunofluorescence (CyCIF): 53 channels over 13 cycles, of which 11 are kept here. It comes from a BRCA2 mutation carrier, 64 at diagnosis, whose risk-reducing surgery found an incidental STIC in the right fallopian tube. Each figure can be panned and zoomed.

Paper: Kader T, Lin J-R, Hug CB, et al. Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma. Cancer Discovery 15, 1180–1202 (2025). doi:10.1158/2159-8290.CD-24-1366

The Lesion Carries the p53 Signature of Ovarian Cancer

Nearly every high-grade serous cancer carries a TP53 mutation, which shows in tissue as strong p53 staining in the cell nucleus. Here a stretch of tube lining with p53 in almost every nucleus (red on white epithelium) runs into normal lining where p53 stops: the boundary between the lesion and the healthy tube is visible in one field. Dividing cells (Ki67, green) are scattered through the lesion.

Precursor Cells Raise MHC Class I, Including HLA-E

MHC class I molecules present a cell's proteins to the immune system. HLA-E, an unusual member of the family, can also restrain killer cells. The same tissue, now showing HLA-E (red) and HLA-A (green): where both are high they appear yellow, and that is brightest in the lesion, well above the normal lining further along the tube. Blood vessels are HLA-positive too, as expected.

Micronuclei Mark Chromosomal Instability in the Lesion

When chromosomes are missegregated, fragments end up in micronuclei outside the main nucleus, a hallmark of chromosomal instability. BANF1 binds the DNA of these micronuclei. This view opens zoomed in on the lesion, about a millimeter across, where BANF1 dots (red) line the precursor epithelium while the tissue around it has few.

About These Charts

The lesion's position on this slide was located for this page from the p53 staining of the tube lining (the strongest p53 in epithelium on the slide, which ends where normal lining begins); the authors' own annotation of it was not available.

The views show an 11-marker, 4.9 × 4.9 mm crop of slide LSP11060 at full resolution (0.65 µm per pixel), read from the HTAN images in the Discovery Lab TRE (9df73c33; crop 35ea1694) and converted for viewing with Spatial Data Studio (f2b58ef9). Brightness is set per marker from its 0.1st to 99.9th percentile over tissue.