Abstract
Risk reclassification of endometrial cancer according to molecular profiling: UK single centre experience.
Author
person
Narda Kebaier Ep Chaabouni
The Royal Marsden Hospital, London, London, United Kingdom
info_outline
Narda Kebaier Ep Chaabouni, Katherine Vroobel, Ayoma Attygalle, Paula Proszek, Susan Lalondrelle, Alexandra Taylor, Angela Joy George
Full text
Authors
person
Narda Kebaier Ep Chaabouni
The Royal Marsden Hospital, London, London, United Kingdom
info_outline
Narda Kebaier Ep Chaabouni, Katherine Vroobel, Ayoma Attygalle, Paula Proszek, Susan Lalondrelle, Alexandra Taylor, Angela Joy George
Organizations
The Royal Marsden Hospital, London, London, United Kingdom, The Royal Marsden NHS Foundation Trust, London, United Kingdom, The Royal Marsden Hospital, London and Surrey, United Kingdom, The Royal Marsden Hospital NHS Foundation Trust, London, Londom, United Kingdom, The Royal Marsden NHS Foundation Trust, Surrey, United Kingdom, The Royal Marsden Hospital, London, United Kingdom, Royal Marsden Hospital, London, United Kingdom
Abstract Disclosures
Research Funding
No funding received
None.
Background:
Endometrial cancer (EC) ranks second among gynaecological malignancies worldwide. Traditionally, adjuvant treatment recommendation was based on risk stratification based on clinicopathological data. The Cancer Genome Atlas (TCGA) defined four distinct and prognostically significant molecular subgroups. Recent international guidelines recommend integrating molecular classification into risk stratification. The aim of our study was to evaluate the distribution of molecular groups in our population and its impact on treatment decision.
Methods:
Retrospective cohort study including all newly diagnosed endometrial cancer cases treated at the Royal Marsden Hospital between July 2020 and May 2022. Tumour specimens underwent next generation sequencing (NGS) of a two hundred gene panel including POLD1, POLE; MMR proteins and TP53; concordance for the latter two assessed also by immunohistochemistry (IHC). Risk stratification according to ESMO guidelines and following molecular classification was reviewed for each case and its potential impact on treatment decision.
Results:
121 patients were included. POLE mutated tumours comprised 14 cases (11.6%), MSI hypermutated 24 cases (19.8 %), copy number high 36 cases (29.8%), copy number low 45 cases (37.2%) and 2 cases (1.6%) where classified as NOS (not otherwise specified). According to clinicopathological data, 39 tumours were categorised as low risk, 14 tumours as intermediate risk, 15 tumours as high-intermediate risk, 39 tumours as high risk and 14 were advanced/metastatic. According to final prognostic group when molecular profile was integrated 8.3 % (n = 10) of cases were reclassified: 8 cases were down staged (2 high, 3 high-intermediate, 3 intermediate) to low-risk category due to POLE mutations. 2 cases were upstaged from high-intermediate to high-risk category (copy number high tumours). There were no shifts noted in the low risk (based on clinicopathological data) prognostic group. One further case in the high-risk category (stage III, gr3 endometrioid tumour with substantial LVSI) was found to be POLE mutated and may be reclassified as low risk. For the 10 cases that were reclassified, adjuvant treatment recommendations may have been adjusted according to the most recent ESMO guidelines.
Conclusions:
Molecular classification refines traditional risk classification of EC and may change treatment recommendation in a non-negligible proportion of patients. Efforts should be made to implement molecular analysis in routine clinical practice to guide appropriate treatment.
4 organizations
4 drugs
4 targets
Organization
The Royal Marsden HospitalOrganization
The Royal Marsden Hospital NHS Foundation TrustDrug
POLD1Drug
POLE P286RDrug
MMR proteinsDrug
TP53Target
MMR proteinsTarget
POLD1Target
TP53Target
POLE P286R