Endometrial cancer focused gene panel

Also known as: Endometrial panel, CTNNB1, PIK3CA, POLE, TP53

Test category:

Oncology – Endometrial carcinoma

Use of test

Purpose:
The endometrial cancer focused gene panel includes genes relevant to prognosis in endometrial carcinoma – POLE, TP53 and CTNNB1. It also includes PIK3CA, which is commonly mutated in endometrial carcinoma and may be a target for clinical trial enrolment.
Utility:

Endometrial carcinoma can be classified into four molecular subgroups, with distinct prognostic outcomes, based on analysis of genomic data from The Cancer Genome Atlas (TCGA). This prognostic information may be useful to assist with informed decision making and treatment planning in endometrial cancer.

The TCGA classification can be recapitulated using three biomarkers: POLE exonuclease domain mutation status, mismatch repair gene immunohistochemistry, and p53 immunohistochemistry. Considered together, these three markers can accurately identify the molecular subgroup; this combination is termed the “ProMisE” classifier (Proactive Molecular risk classifier for Endometrial Cancer).

The endometrial cancer focussed panel provides POLE mutation status, and also sequences exons 4-9 of TP53, as additional information to p53 immunohistochemistry. Relevant hotspot mutations in CTNNB1 are also sequenced, as emerging evidence suggests that these may provide useful prognostic information for tumours in the “no specific molecular profile” subgroup. 

Note that to determine the full ProMisE classifier status, the POLE mutation result needs to be considered in the context of p53 and mismatch repair immunohistochemistry. These tests are available through the local Sonic pathology practice.

Finally, activation of the PI3K/AKT/mTOR pathway is known to occur in some endometrial cancers. Activating mutations in PIK3CA are a common mechanism for activation of this pathway. Presence of an activating PIK3CA mutation may provide options for enrolment in clinical trials in the advanced/metastatic setting.  

This test can be expanded to a full Find It panel that simultaneously evaluates the mutation status of tumour DNA at more than 140 well-characterised positions (hotspots) and more than 20 exons in no less than 30 cancer-associated genes.

Ethical considerations:

This assay is designed to detect non-heritable mutations. It does typically not raise issues of ethics or consent that are different from most other investigations ordered in the routine care of a patient.

Methodology:

Targeted analysis of clinically relevant mutations in CTNNB1 (codons 32-45), PIK3CA (codons 452-549 and 1043-1049), POLE (exons 9-14), and TP53 (exons 4-9).  This assay detects targeted single nucleotide variants and insertion/deletion mutations (of up to 24 base pairs in size). Fusion genes and copy number variants will not be detected. Very low level targeted variants (<5% variant allele frequency) may not be detected.

For further details, please refer to the description of the full Find It panel.

Requesting the test

Ordering:

This test is usually requested by a surgeon or oncologist. Please use the specific request form (see link below).

Request Form:

Download the somatic mutation request form.

Sample required:

Formalin-fixed, paraffin embedded tissue (FFPE) - 15 sections of 4 uM thickness, dried overnight at 37°C onto charged/coated slides.

Special instructions:

Please label each slide with patient and block identifiers plus number them sequentially 1-15. Stain slides 1 and 15 with H&E and leave slides 2 to 14 unstained. The request should be accompanied by the somatic mutation request form (above) and a copy of the original histopathology report.

Turnaround time:

7 business days from receipt of sections by the testing laboratory.

Price:

$350 for Endometrial cancer panel.

Rebate:

No MBS rebate is available for the endometrial cancer focussed panel.

 

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