title: Implementation of tumor testing for lynch syndrome in endometrial cancers at a large academic medical center.
abstract: OBJECTIVE
  Lynch syndrome (LS) is a hereditary condition that increases the risk for endometrial and other cancers. Recognizing women at risk for LS based on personal/family history is burdensome and imprecise. Tumor testing using microsatellite instability (MSI) testing and immunohistochemistry (IHC) for mismatch repair protein expression can be an effective strategy for identifying potential LS in patients presenting with colorectal or endometrial cancer. Here we describe our experience implementing a screening program for endometrial cancers.
  
  
  METHODS
  Endometrial cancers diagnosed ≤50 years or those with suspicious personal history or histopathologic features were screened with MSI/IHC, June 2009-June 2011. Criteria were later (July 2011-July 2012) expanded to patients diagnosed <60 years, or at any age with suspicious features, and finally (after August 2012) universal screening was implemented. Screening techniques began with both MSI and IHC for every tumor, and later converted to IHC for two proteins, and MLH1 promoter methylation analysis when indicated. A genetic counselor contacted patients directly to offer genetic counseling appointments.
  
  
  RESULTS
  Two hundred and forty-five endometrial cancers (average age, 57 years) were screened. Sixty-two patients (25%) had abnormal results, and 42 patients were referred for genetic counseling. Of the 42 patients, 34 underwent genetic counseling, 28 pursued genetic testing, and 11 were diagnosed with LS. When age and pathology criteria were used, 27 eligible cases were overlooked for screening and 3 cases of LS were found only because a clinician requested screening.
  
  
  CONCLUSIONS
  Universal screening of endometrial cancers for LS is practical and successfully implemented with collaboration among genetic counselors, gynecologic oncologists, and pathologists.
authors.affiliation: Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Moline
authors.forename: Haider
authors.initials: H
authors.lastname: Mahdi
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Charles
authors.initials: C
authors.lastname: Biscotti
authors.forename: Andres A
authors.initials: AA
authors.lastname: Roma
authors.forename: Brandie
authors.initials: B
authors.lastname: Heald
authors.forename: Peter G
authors.initials: PG
authors.lastname: Rose
authors.forename: Chad
authors.initials: C
authors.lastname: Michener
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
mesh_terms: D000046:Academic Medical Centers; D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D045643:DNA Repair Enzymes / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D055088:Early Detection of Cancer / Q000379:methods; D016889:Endometrial Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D005260:Female; D005817:Genetic Counseling; D006801:Humans; D007150:Immunohistochemistry; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes