Early Precursor Escape and High-Grade Serious Carcinoma
Abstract
A serous carcinogenesis sequence has been described in the distal fallopian tube but a significant proportion of extra uterine high-grade serous carcinomas (HGSCs) are not associated with an "early" carcinoma in the fimbria. To explain this discrepancy, a hypothesis of "precursor escape" has been proposed, by which exfoliated cells from early serous precursors (ESPs) escape the tube and later undergo malignant transformation in the peritoneal cavity, leading to "primary peritoneal" serous carcinomas. The aims of this proposal were to identify mutations in exfoliated epithelial cells from peritoneal washings, further link HGSCs to ESPs by shared mutations and establish lineage between ESPs and HGSCs by whole exome sequencing. Flow cytometric enrichment of washings for epithelial cells generally yielded small numbers of cells but a TP53 mutation was identified by sequence analysis in one, supporting a model by which mutated epithelial cells escaped into the peritoneal cavity. Further sequence analysis of ESPs and paired HGSCs identified shared TP53mutations, although there were technical limitations imposed by small samples. Additional cases material was analyzed following laser capture microdissection and the results are pending, as are whole exome sequencing studies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2021
- Accession Number
- AD1178567
Entities
People
- Christopher P Crum
Organizations
- Brigham and Women's Hospital