Iatrogenic endometriosis harbors somatic cancer-driver mutations

V Lac; TH Praetorius; L Verhoef; R Aguirre-Hernandez; TM Nazeran; B Tessier-Cloutier; N Orr; H Noga; J Khattra; M Koebel; HM Horlings; F Kommoss; SY Brucker; J Pasternak; PJ Yong; DG Huntsman; S Kommoss; MS Anglesio; B Krämer

doi:10.1055/s-0038-1671405

Geburtshilfe und Frauenheilkunde, Table of Contents

Geburtshilfe Frauenheilkd 2018; 78(10): 215
DOI: 10.1055/s-0038-1671405

Poster

Freitag, 02.11.2018

Operative Gynäkologie, Urogynäkologie II

Georg Thieme Verlag KG Stuttgart · New York

Iatrogenic endometriosis harbors somatic cancer-driver mutations

V Lac

¹British Columbia Cancer Agency, Department of Molecular Oncology, Vancouver, Kanada

²University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, Kanada

,

TH Praetorius

³Universitätsklinikum Tübingen, Department für Frauengesundheit, Tübingen, Deutschland

⁴University of British Columbia, Department of Obstetrics and Gynecology, Vancouver, Kanada

,

L Verhoef

⁵Netherlands Cancer Institute, Amsterdam, Niederlande

,

R Aguirre-Hernandez

⁶Contextual Genomics, Vancouver, Kanada

,

TM Nazeran

¹British Columbia Cancer Agency, Department of Molecular Oncology, Vancouver, Kanada

²University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, Kanada

,

B Tessier-Cloutier

²University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, Kanada

⁷Vancouver General Hospital, Department of Anatomical Pathology, Vancouver, Kanada

,

N Orr

⁴University of British Columbia, Department of Obstetrics and Gynecology, Vancouver, Kanada

,

H Noga

⁴University of British Columbia, Department of Obstetrics and Gynecology, Vancouver, Kanada

⁸British Columbia Women's Hospital and Health Centre, BC Women's Centre for Pelvic Pain & Endometriosis, Vancouver, Kanada

,

J Khattra

⁶Contextual Genomics, Vancouver, Kanada

,

M Koebel

⁹University of Calgary, Department of Pathology and Laboratory Medicine, Calgary, Kanada

,

HM Horlings

⁵Netherlands Cancer Institute, Amsterdam, Niederlande

,

F Kommoss

¹⁰Medizin Campus Bodensee, Institut für Pathologie, Friedrichshafen, Deutschland

,

SY Brucker

³Universitätsklinikum Tübingen, Department für Frauengesundheit, Tübingen, Deutschland

,

J Pasternak

³Universitätsklinikum Tübingen, Department für Frauengesundheit, Tübingen, Deutschland

,

PJ Yong

⁴University of British Columbia, Department of Obstetrics and Gynecology, Vancouver, Kanada

⁸British Columbia Women's Hospital and Health Centre, BC Women's Centre for Pelvic Pain & Endometriosis, Vancouver, Kanada

,

DG Huntsman

¹British Columbia Cancer Agency, Department of Molecular Oncology, Vancouver, Kanada

²University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, Kanada

⁶Contextual Genomics, Vancouver, Kanada

,

S Kommoss

³Universitätsklinikum Tübingen, Department für Frauengesundheit, Tübingen, Deutschland

,

MS Anglesio

²University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, Kanada

⁴University of British Columbia, Department of Obstetrics and Gynecology, Vancouver, Kanada

,

B Krämer

³Universitätsklinikum Tübingen, Department für Frauengesundheit, Tübingen, Deutschland

› Author Affiliations

Abstract

Full Text

Objectives:

Endometriosis is a common gynecological disease and precursor of clear cell and endometrioid ovarian carcinomas. We recently demonstrated that one form of endometriosis with little malignant potential, deep infiltrating endometriosis (DE), harbours recurrent somatic cancer-driver mutations. The prevalence of these mutations in other forms of endometriosis is not known. We sought to investigate this by examining other forms of endometriosis unlikely to undergo transformation. Particularly, we examined an iatrogenic form of endometriosis (incisional endometriosis; IE) where the uterine origin of cells is well accepted.

Materials and methods:

Endometriosis specimens were macrodissected from archival tissue collected from 40 women with IE and 36 women with DE. A hypersensitive cancer hotspot sequencing panel was used to identify mutations, which were validated using droplet digital PCR. PTEN and ARID1A immunohistochemistry were performed as surrogates for somatic events resulting in functional loss of respective proteins.

Results:

Somatic cancer-driver events were detected in 27.5% IE cases and 38.9% DE cases, including hotspot mutations in KRAS, ERBB2, PIK3CA, and CTNNB1. Heterogeneous PTEN loss occurred at similar rates in IE and DE (6/40 versus 5/36 respectively), whereas ARID1A loss only occurred in one DE case.

Conclusions:

Despite differing mechanisms of dissemination, somatic cancer-driver events are a common feature of IE and DE. These alterations affected components of the MAPK/RAS or PI3K-Akt-mTOR pathways, which may be important in the growth and survival of endometriosis ectopically. Examination of similar somatic events in eutopic endometrium and other forms of endometriosis, in particular endometriomas (commonly linked to malignancy) are warranted.