Prospective evaluation of DNA mismatch repair protein expression in primary endometrial cancer

Gynecol Oncol. 2009 Sep;114(3):486-90. doi: 10.1016/j.ygyno.2009.05.026. Epub 2009 Jun 10.


Objectives: Immunohistochemical (IHC) stains for mismatch repair (MMR) proteins help screen for Lynch syndrome and identify microsatellite unstable colorectal carcinomas, providing prognostic information. It has been suggested that colorectal and endometrial carcinomas should be screened routinely for a MMR defect, but data are lacking on the practical application of this policy. We report our experience with the prospective evaluation of MMR protein expression in endometrial cancer.

Methods: All cases of primary endometrial cancer at a single institution regardless of age, family history or histologic features were prospectively stained for the MMR proteins MLH1, MSH2, MSH6 and PMS2. Clinical and pathologic correlates were collected from the medical record.

Results: A total of 140 endometrial cancer cases were studied. Over 90% of cases were of endometrioid histology. 119 patients had stage I/II disease, and 21 stage III/IV. Nineteen percent of patients were < age 50. Overall, there was loss of 1 or more MMR proteins in 30 patients (21%), including MLH1 and PMS2 in 24, MSH2 and MSH6 in 4, and MSH6 in 2 patients. None of the patients met clinical criteria for Lynch syndrome. However, using MMR protein expression, age and family history, 11% of patients were referred for genetic counseling. Of these patients, three (20%) scheduled an appointment: one canceled and two tested negative.

Conclusions: Prospective staining for MMR proteins is feasible and allows for primary triage for the evaluation of Lynch syndrome in women with endometrial cancer. However, acceptance of genetic consultation and testing is surprisingly low and deserves further investigation.

MeSH terms

  • Adaptor Proteins, Signal Transducing / biosynthesis
  • Adenosine Triphosphatases / biosynthesis
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Endometrioid / enzymology
  • Carcinoma, Endometrioid / genetics
  • Carcinoma, Endometrioid / pathology
  • DNA Mismatch Repair
  • DNA Repair Enzymes / biosynthesis*
  • DNA-Binding Proteins / biosynthesis
  • Endometrial Neoplasms / enzymology*
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology
  • Female
  • Humans
  • Middle Aged
  • Mismatch Repair Endonuclease PMS2
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / biosynthesis
  • Neoplasm Staging
  • Nuclear Proteins / biosynthesis
  • Prospective Studies


  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • G-T mismatch-binding protein
  • MLH1 protein, human
  • Nuclear Proteins
  • Adenosine Triphosphatases
  • PMS2 protein, human
  • MSH2 protein, human
  • Mismatch Repair Endonuclease PMS2
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • DNA Repair Enzymes