Other Biomarkers in OC
Other biomarkers in OC can help inform treatment decisions, determine cancer risk, and predict disease recurrence.1-3
dMMR and MSI-H
In healthy cells, mismatch repair (MMR) proteins correct certain errors in DNA replication.4 A deficiency in MMR (dMMR) causes mutations to accumulate, which may increase the TMB and thereby enhance response to immunotherapy.4
One way to assess dMMR is by measuring microsatellite instability (MSI).4
Microsatellites are short, repetitive DNA sequences that have a high susceptibility to errors typically repaired by MMR proteins.4
Prevalence: ≈10% of patients with OC have dMMR5
For patients with recurrent OC, NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend IHC for DNA MMR proteins (MLH1, MSH2, MSH6, and PMS2) or MSI testing via PCR.6
Homologous recombination is critical for the repair of DNA damage, including DNA double-strand breaks; therefore, mutations in homologous recombination repair (HRR) genes can increase the risk of developing cancer.2,7
Prevalence: Up to 50% of OCs may be associated with HRR deficiency, including BRCA mutations2
NCCN Guidelines® recommend considering testing for homologous recombination deficiency in patients with recurrent OC.6
Multigene panels are available to test for pathogenic or likely pathogenic mutations associated with inherited susceptibility to cancer.8
NCCN Guidelines suggest testing for the following mutations in patients with OC because they are associated with a risk of developing OC8:
*Associated with increased risk of nonepithelial OC.
To optimize turnaround time and cost efficiency, some laboratories offer testing for BRCA mutations first, then automatically reflex to a larger multigene panel if the BRCA mutation test returns negative results.12
Different multigene panels may test for different sets of genes; therefore, panel tests should be chosen carefully.8
Biomarkers for recurrence
For some patients, serum CA-125 levels may be predictive of disease recurrence after primary therapy.3 As part of monitoring and follow-up after primary therapy, NCCN Guidelines recommend testing for elevated CA-125 levels if levels were initially elevated at diagnosis.6
For patients who have complete remission, treatment of biochemical relapse (serially rising CA-125 without clinical relapse) is controversial. For patients in clinical remission, the pros and cons of CA-125 monitoring should be discussed.6
BRCA, breast cancer susceptibility gene; BRIP1, BRCA1 interacting protein C-terminal helicase 1; dMMR, deficient mismatch repair; EPCAM, epithelial cell adhesion molecule; FDA, Food and Drug Administration; HRR, homologous recombination repair; IHC, immunohistochemistry; MLH1, MutL homolog 1; MMR, mismatch repair; MSH2, MutS homolog 2; MSH6, MutS homolog 6; MSI-H, microsatellite instability–high; NCCN, National Comprehensive Cancer Network; OC, ovarian cancer; PCR, polymerase chain reaction; PMS2, PMS1 homolog 2; RAD51C, RAD51 paralog C; RAD51D, RAD51 paralog D; STK11, serine/threonine kinase 11; TMB, tumor mutational burden.
References: 1. Keytruda [prescribing information]. Whitehouse Station, NJ: Merck & Co, Inc; 2019. 2. Gee ME et al. J Ovarian Res. 2018;11(1):50. 3. Sarojini S et al. J Oncol. 2012;2012:709049. 4. Viale G et al. Biomed Res Int. 2017;2017:4719194. 5. Murphy MA et al. Int J Cancer. 2011;129(8):1914-1922. 6. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer V1.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed March 16, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 7. Li X et al. Cell Res. 2008;18(1):99-113. 8. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic V1.2020. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed March 3, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 9. Tayama S et al. Oncotarget. 2017;8(27):44312-44325. 10. Frey MK et al. Gynecol Oncol Res Pract. 2017;4:4. 11. Pappas K et al. Mol Cancer Res. 2017;15(8):1051-1062. 12. Stanislaw C et al. Cancer Biol Med. 2016;13(1):55-67.