Abstract AP01: LINEAGE CONTINUITY BETWEEN EARLY TUBAL SEROUS PROLIFERATIONS (ESPS/STILS) AND DISSEMINATED HIGH-GRADE SEROUS CARCINOMAS: A MODEL FOR “PRECURSOR ESCAPE”

It is now well known that the distal fallopian tube is a site of origin for many high-grade serous carcinomas (HGSCs). HGSCs are thought to arise via intra-peritoneal spread of tumor cells from serous tubal intra-epithelial carcinomas (STICs) that share identical TP53 mutations. However, a dualistic model of pathogenesis might be indicated because many HGSCs are not associated with STICs and their site(s) of origin is unclear. This fact has important implications for both screening and cancer preventive strategies. In addition to STICs, the tube also hosts TP53 mutation-positive early serous proliferations (ESPs) that comprise a morphologic spectrum ranging from p53 signatures to serous tubal intraepithelial lesions (STILs). ESPs are more common than STICs and are not considered malignant; however, they are often the only abnormality found in fallopian tubes of women with HGSCs. The purpose of this study was to determine if a genetic relationship exists between isolated ESPs and concurrent HGSCs in the absence of STIC. Fallopian tubes from 32 HGSCs without a co-existing STIC on initial review were exhaustively and serially sectioned. The presence of either occult STIC or ESP in serial sections was documented and DNAs from tissues containing ESPs, cancers and normal control epithelia were interrogated for TP53 mutations by targeted amplicon-based sequencing with average coverage reads >4000 across DNA replicate samples. Serial sectioning unearthed a STIC in 3 of 32 (9.3%) and ESPs in 12 (37.5%). Four of 12 ESPs (33.0%) shared an identical TP53 mutation with the concurrent cancer at an allele frequency ≥5%. An additional 5 ESPs (41.7%) also shared identical TP53 mutations with concurrent cancers at a lower ( Citation Format: Thing Rinda Soong, MD, PhD, MPH, Brooke E. Howitt, MD, Alexander Miron, PhD, Neil Horowitz, MD, Frank Campbell, PhD, Colleen M. Feltmate, MD, Michael G. Muto, MD, Ross S. Berkowitz, MD, Marisa R. Nucci, MD, Wa Xian, PhD, Christopher P. Crum, MD. LINEAGE CONTINUITY BETWEEN EARLY TUBAL SEROUS PROLIFERATIONS (ESPS/STILS) AND DISSEMINATED HIGH-GRADE SEROUS CARCINOMAS: A MODEL FOR “PRECURSOR ESCAPE” [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr AP01.