testing strategies for Lynch syndrome in people with endometrial cancer

Last edited 10/2020 and last reviewed 06/2021

Lynch syndrome is an inherited condition that increases the risk of certain types of cancer, including endometrial and colorectal cancer

  • risk of endometrial cancer if Lynch syndrome-associated colorectal cancer
    • evidence suggests that approximately one quarter of women diagnosed with Lynch syndrome-associated colorectal cancer developed endometrial cancer within 10 years (1)

  • risk of other cancers if Lynch syndrome-associated endometrial cancer (2)
    • Lynch syndrome is an autosomal dominantly inherited disorder caused by germline mutations in DNA mismatch repair (MMR) genes
    • following endometrial cancer, women carrying MMR gene mutations had the following 20-year risks of other cancer cancers:
      • colorectal cancer (48%, 95% confidence interval [CI] = 35% to 62%);
      • cancer of the kidney, renal pelvis, or ureter (11%, 95% CI = 3% to 20%);
      • urinary bladder cancer (9%, 95% CI = 2% to 17%);
      • and breast cancer (11%, 95% CI = 4% to 19%).
      • compared with the general population, these women were at statistically significantly elevated risks of colorectal cancer (standardized incidence ratio (SIR) = 39.9, 95% CI = 27.2 to 58.3), cancer of the kidney, renal pelvis, or ureter (SIR = 28.3, 95% CI = 11.9 to 48.6), urinary bladder cancer (SIR = 24.3, 95% CI = 8.56 to 42.9), and breast cancer (SIR = 2.51, 95% CI = 1.17 to 4.14)
      • this study revealed that, over a 20-year period, Lynch syndrome-associated endometrial cancer there was increased subsequent risk of colorectal cancer, urinary tract cancers, bladder cancer, and breast cancer

  • NICE recommends testing for Lynch syndrome after a colorectal cancer diagnosis
  • however endometrial cancer is often the first cancer that people with Lynch syndrome will have
    • so, Lynch syndrome could be identified earlier if tests are done after a diagnosis of endometrial cancer
    • if Lynch syndrome is diagnosed, treatment and surveillance can be offered to reduce the risk of having another Lynch syndrome-associated cancer (in particular colorectal cancer) or identify it earlier
      • genetic testing for Lynch syndrome can also be offered to relatives with the aim of preventing Lynch syndrome-associated cancer developing or detecting it at an early stage.

NICE suggest (2):

  • offer testing for Lynch syndrome to people who are diagnosed with endometrial cancer. Use immunohistochemistry (IHC) to identify tumours with mismatch repair (MMR) deficiency:
    • if IHC is abnormal with loss of MLH1, or loss of both MLH1 and PMS2 protein expression, do MLH1 promoter hypermethylation testing of tumour DNA. If MLH1 promoter hypermethylation is not detected, offer germline genetic testing to confirm Lynch syndrome
    • if IHC is abnormal with loss of MSH2, MSH6 or isolated PMS2 protein expression, offer germline genetic testing to confirm Lynch syndrome
  • healthcare professionals should inform people about the possible implications of test results for both themselves and their relatives, and give support and information. Discussion of genetic testing and obtaining consent should be done by a healthcare professional with appropriate training

Identifying Lynch syndrome at the point of endometrial cancer diagnosis could:

  • prevent other cancers in people with Lynch syndrome (such as colorectal cancer) through increased surveillance and strategies to reduce risk
  • help to identify relatives with Lynch syndrome, to reduce their risk of Lynch syndrome-associated cancers or increase early detection of cancer
  • help relatives diagnosed at an early age to consider family planning and, if they wish, have risk-reducing interventions, for example, a hysterectomy.

Reference:

Related pages:

Lynch syndrome

endometrial cancer and Lynch syndrome