ProMisE is a new molecular method of categorising endometrial cancers (EC). This Bulletin outlines the technical basis of the ProMisE classification of, and is directed at doctors involved in, the diagnosis and management of gynaecological cancer.
For a discussion of the clinical implications of this classifier, please click here.
POLE and ProMisE
In 2013, analysis of The Cancer Genome Atlas (TCGA) identified four molecular subclasses of EC, with distinct prognostic differences. The categories were POLE ultra-mutated, MSI (microsatellite instability) hyper-mutated, copy-number low and copy-number high.
ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) is a classification system based on TCGA that utilises pragmatic methods to identify these genomic subgroups. Classification is feasible on formalin-fixed, paraffin-embedded (FFPE) material and assigns patients with EC to one of four groups, based on a combination of immunohistochemistry for mismatch repair (MMR) proteins (encoded by the genes MLH1, PMS2, MSH2 and MSH6), sequencing for POLE mutation and immunohistochemistry for the p53 protein. Utilising the classifier, EC are classified into:
p53 wild type (p53-wt); also termed NSMP (no specific molecular profile)
p53 mutant (p53-abn)
Ref: Talhouk A, McConechy MK, Leung S, et al. Cancer. 2017; 123(5):802–813
The characteristics of each molecular subtype according to TCGA criteria and subsequent post-TCGA publications are summarised in the Table. References are available here.
LVSI: lymphovascular space invasion; MELF microcystic elongated and fragmented type of invasion; TILs: tumour-infiltrating lymphocytes; BMI: body mass index; IHC: immunohistochemistry; MSI: microsatellite instability *These are proposed treatment options in recurrent and/or metastatic disease currently being explored.
The ProMisE prognostic model may be further refined by exploring Intra-class heterogeneity, particularly regarding mutations in the CTNNB1 and L1CAM genes in the p53-wt category.
The cost for next-generation sequencing analysis of markers for EC, including POLE mutations, is presented here. Mismatch repair and p53 IHC are required for the ProMisE genomic classifier. Please contact your local Sonic Healthcare pathology practice to arrange. Additional charges may apply. Medicare rebates are not available.
The turnaround time is up to 10 business days, and results can be accessed electronically via Sonic Dx, by fax, or by phone.