Diagnosing Lynch syndrome in patients with endometrial cancer


Screening based solely on family history isn't sufficient enough, so new research suggests incorporating these additional tests into your screening practices.

Genetic Testing

©NicoElNino - shutterstock.com

A systematic search of online databases found that 43% of patients with endometrial cancer diagnosed with Lynch syndrome via tumor testing would have been missed by family history-based screening alone.

The comprehensive search in the journal Cancer initially identified 4,400 publications dating back to 1986, of which 29 peer-reviewed studies met inclusion criteria and were analyzed. 

In total, 6,649 patients with endometrial cancer were identified and 206 (3%) were confirmed to have Lynch syndrome.

Read more on Lynch syndrome: Keys to identifying Lynch syndrome

“Early detection of the associated germline genetic mutations of this inherited cancer syndrome can help initiate early surveillance and risk-reducing surgery, which can ultimately decrease cancer-related morbidity and mortality across a population,” said primary author Ryan Kahn, MD, MHS, an ob/gyn resident at New York-Presbyterian Weill Cornell

Universal tumor testing through immunohistochemistry staining for mismatch repair (MMR) proteins and microsatellite instability is now recommended for all colorectal and endometrial cancers. 

“However, there has been minimal literature demonstrating results of this testing across a large population,” Dr. Kahn told Contemporary OB/GYN. “We wanted to conduct a meta-analysis to evaluate the outcomes of MMR immunohistochemistry, mutL homolog 1 (MLH1) methylation and microsatellite instability analysis among patients with endometrial cancer.”

Of the 5,917 patients who underwent tumor immunohistochemistry (IHC), 28% had abnormal IHC staining. Similarly, of the 3,140 patients who underwent microsatellite instability analysis, 31% had abnormal results. 

Overall, weighted prevalence of Lynch syndrome germline mutations among patients with endometrial cancer was 15% with deficient IHC staining and 19% with positive microsatellite instability analysis. 

In the group with abnormal MLH1 staining, methylation testing is recommended to assess for epigenetic changes not attributable to germline mutations. 

Of the 1,159 patients who exhibited loss of MLH1, 13.7% were MLH1methylation–negative, and 32 demonstrated a germline MLH1 mutation: 2.8% of all absent MLH1staining cases and 22.4% of all MLH1 methylation–negative cases. 

“Previous studies have demonstrated the sensitivities and specificities of these screening methods,” Dr. Kahn said. “But our results help demonstrate how effective they can be on a large scale in diagnosing Lynch syndrome.”

The authors were surprised to discover such high rates of abnormal tumor IHC in endometrial cancer. “This information is useful when counseling patients about their expectations for outcomes with this testing,” Dr. Kahn said.

The authors were most surprised, though, to find that tumor typing among endometrial cancers helped diagnose up to 43% of patients that would have been missed by family history-based screening alone.

“We hope our results will help practitioners evaluate abnormal results in the context of Lynch syndrome and aid them in patient counseling,” Dr. Kahn said. The authors equally anticipate that this study will demonstrate how important tumor testing is in endometrial cancer patients in order to help further encourage and improve the uptake of these methods.

Many of the studies used for analysis included a substantial number of patients who demonstrated abnormal tumor testing, but did not subsequently undergo genetic testing. 

“Determining why patients choose not to undergo genetic testing and why some are lost to follow-up will help improve uptake,” Dr. Kahn said.


Several ongoing studies at Weill Cornell Medicine are exploring the barriers that prevent patients from undergoing genetic testing. “Ultimately, these studies aim to improve the access and uptake of both genetic testing and screening,” Dr. Kahn said.


Dr. Kahn reports no relevant financial disclosures.

Related Content
© 2024 MJH Life Sciences

All rights reserved.