This document provides guidelines for assessing and referring patients with endometrial cancer for genetic testing. It outlines the immunohistochemistry pathway for identifying DNA mismatch repair deficiencies. It specifies that if testing finds loss or abnormal staining of MLH1/PMS2 genes, reflex testing for MLH1 promoter methylation will be done, and certain abnormal staining results will require referral to clinical genetics for further assessment. It also provides referral criteria for patients who answer yes to family history questions, cannot be determined to meet testing criteria, are children, or need further discussion about genetic testing.

1. Patient with confirmed endometrial cancer with histology available
Refer to Clinical
Genetics
Send patient details, result and
histology report to
cancergenetics.stg@nhs.net
Other histopathological
subtypes
Adenocarcinoma
High grade serous
Refer to clinical genetics
if concerned about
personal or family history
only
IHC pathway
Immunohistochemistry (IHC) pathway:
• Pathology will undertake reflex mismatch repair immunohistochemistry (MMR-
IHC) analysis
• If loss / abnormal staining of MLH1/PMS2, pathology will send reflex MLH1
promotor hypermethylation testing directly to lab
• If loss / abnormal staining of MSH2/MSH6, clinical treating team to refer to
Genetics
• If loss / abnormal staining of isolated PMS2, clinical treating team to refer to
Genetics
• If loss / abnormal staining of MLH1/PMS2 AND absent MLH1 promotor
hypermethylation, clinical treating team to refer to Genetics
Patient with endometrial
cancer and:
• Answers “yes” to any questions on
family history screening
questionnaire
• Unable to establish if patient meets
testing criteria
• Children (<18 years)
• Patient is unsure about testing or
needs further discussion
Refer to clinical genetics
GENETIC ASSESSMENT/TESTING PATHWAYS: ENDOMETRIAL CANCER
Complete family history screening questionnaire
SOUTH WEST THAMES REGIONAL GENETICS SERVICE
EC Protocol v1 180521