Molecular analysis of high-grade serous ovarian carcinoma with and without associated serous tubal intra-epithelial carcinoma

Robert A. Soslow,Jennifer Ducie,Robert J. Kurman,Patricia A. Shaw,Narciso Olvera,Ie-Ming Shih,Fanny Dao,Douglas A. Levine,Leslie Cope,Michael Considine

doi:10.1038/s41467-017-01217-9

Abstract

Many high-grade serous carcinomas (HGSCs) of the pelvis are thought to originate in the distal portion of the fallopian tube. Serous tubal intra-epithelial carcinoma (STIC) lesions are the putative precursor to HGSC and identifiable in ~ 50% of advanced stage cases. To better understand the molecular etiology of HGSCs, we report a multi-center integrated genomic analysis of advanced stage tumors with and without STIC lesions and normal tissues. The most significant focal DNA SCNAs were shared between cases with and without STIC lesions. The RNA sequence and the miRNA data did not identify any clear separation between cases with and without STIC lesions. HGSCs had molecular profiles more similar to normal fallopian tube epithelium than ovarian surface epithelium or peritoneum. The data suggest that the molecular features of HGSCs with and without associated STIC lesions are mostly shared, indicating a common biologic origin, likely to be the distal fallopian tube among all cases.

Highlights

Many high-grade serous carcinomas (HGSCs) of the pelvis are thought to originate in the distal portion of the fallopian tube
Ovarian cancer has traditionally been thought to develop from the ovarian surface epithelium (OSE) or cortical inclusion cysts (CICs), but the recent data suggest that a majority of advanced high-grade serous carcinomas (HGSC) likely originate from the epithelium of the distal fallopian tube[1]
With the exception of formal diagnosis, which changes by definition in the presence of Serous tubal intra-epithelial carcinoma (STIC) lesions, there were no differences in key clinical features or survival between patients with or without STIC lesions (Table 1 and Supplementary Fig. 1)

Summary

Introduction

Many high-grade serous carcinomas (HGSCs) of the pelvis are thought to originate in the distal portion of the fallopian tube. The data suggest that the molecular features of HGSCs with and without associated STIC lesions are mostly shared, indicating a common biologic origin, likely to be the distal fallopian tube among all cases. Ovarian cancer has traditionally been thought to develop from the ovarian surface epithelium (OSE) or cortical inclusion cysts (CICs), but the recent data suggest that a majority of advanced high-grade serous carcinomas (HGSC) likely originate from the epithelium of the distal fallopian tube[1]. Alternatives to the tubal hypothesis suggest that the tubal epithelium is colonized in a metastatic manner from the primary ovarian tumor or that some pelvic HGSCs originate from tubal epithelium and others originate from other pelvic structures such as the “secondary Müllerian system”[8] The former has been disproven using studies of telomere length and clonality[9]. As described in detail in “Methods” section, we designed the study with sufficient power to detect most molecular differences in the moderate to large range, reasoning that a negative result would provide strong evidence in support of the single origin theory

Methods

Results

Conclusion