Endometrial Cancer (NGS) Panel

10 unstained sections of tumour and a corresponding H&E-stained histological section, OR 1 paraffin block of tumour 

No

The test is batched and performed every Tuesday. The test itself takes 5 working days to complete. 

KKH

Molecular Pathology

6394 1402 

Mon – Fri: 0800 hrs– 1700 hrs 

No

Molecular Pathology

Background 
Molecular signatures are important parameters for staging, risk stratification, and treatment determination in endometrial cancer. Pathogenic mutations in the POLE and TP53 genes inform molecular classification and staging in the 2023 FIGO endometrial cancer staging system. Pathogenic mutations in the CTNNB1 gene can also be used in risk-stratification in clinical trials for endometrial cancers.   

Purpose of test 
Targeted genetic profiling of the transcribed regions of the POLE, TP53, PIK3CA and CTNNB1 genes using a custom next generation sequencing panel. The reportable variants are as follows:    

POLE: p.P286R, p.V411L, p.S297F, p.S459F, p.A456P, p.F367S, p.L424I, p.M295R, p.P436R, p.M444K and p.D368Y only. 

TP53: All exonic variants. 

PIK3CA: All exonic variants except for 44, 39 and 47 bases in exons 10 (chr3:178,935,973-178,936,147), 12 (chr3:178,937,334-178,937,548) and 13 (chr3:178,937,712-178,937,865) of PIK3CA (NM006218.4) 

CTNNB1: All exonic variants.  

Caveats 
Tumour content must be >50%. DNA quality and concentrations must meet assay requirements. Low tumour content below 50% may result in a false negative result.  

The DNA assay component does not detect variants occurring at allele frequency of less than 5%, exon deletions, and variants in regions for which sequencing coverage is less than 250x.   This test is validated for somatic variants only. Variants identified may include germline variants even though these are not specifically tested for.   

Proficiency testing 
Alternative performance assessment programme.

Reference  

1. León-Castillo A, et al. Interpretation of somatic POLE mutations in endometrial carcinoma. J Pathol. 2020 Mar;250(3): 323-335. 
2. van den Heerik ASVM, et al. PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer. Int J Gynecol Cancer. 2020 Dec;30(12):2002-2007. 
3. Berek JS, et al. FIGO staging of endometrial cancer: 2023. Int J Gynaecol Obstet. 2023 Aug;162(2):383-394. 
4. Naveena S, et al. BAGP POLE NGS testing guidance, v1.2, dated 26 July 2022. 
5. Schultheis AM, et al. TP53 Mutational Spectrum in Endometrioid and Serous Endometrial Cancers. Int J Gynecol Pathol. 2016 Jul;35(4):289-300.  
6. Vermij, L., et al. p53 immunohistochemistry in endometrial cancer: clinical and molecular correlates in the PORTEC-3 trial. Mod Pathol. 2022;35:1475–1483. 
7. Fabrice A, et al. Alpelisib for PIK3CA-Mutated, Hormone Receptor–Positive Advanced Breast Cancer. N Engl J Med. 2019;380:1929-1940.