title: [A new oncogenetic service of counseling and diagnosing for hereditary non-polyposis colorectal cancer (HNPCC)].
abstract: BACKGROUND
  Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant cancer predisposition syndrome associated with a high risk for colorectal cancer (up to 80%), endometrial cancer (up to 60%), and increased risk for other malignancies, mostly ovarian and urinary system tumors. HNPCC is caused by a germline mutation in one of the mismatch repair (MMR) genes, mainly hMLH1, hMSH2 and hMSH6. The tumors present with microsatellite instability (MSI) associated with loss of heterozygosity of the affected gene, and with loss of expression of the gene product. Diagnosis of HNPCC involves tumor testing for MSI, immunohistochemistry staining and germ line mutation analysis of the suspected gene. Proper genetic counseling is based on the synthesis of the clinical, pathological and molecular data. Directed surveillance shows significant reduction in colon cancer incidence, cancer mortality and overall mortality among HNPCC patients.
  
  
  OBJECTIVE
  To establish a multidisciplinary service for patients suspected of having HNPCC.
  
  
  METHODS
  We have established a service which is based on tight collaboration between clinical departments and laboratories. The clinical work-up was conducted by a special oncogenetic clinic and the laboratory service consisted of tissue testing for MSI and immunohistochemistry, denaturing high performance liquid chromatography (DHPLC) for suspected genes, and mutation testing.
  
  
  RESULTS
  The efficiency of detection of patients with HNPCC was high, completed in a multistep process. In the first year of our collaborative work, we have provided genetic counseling to over 100 families and performed suitable tests for 46 families. Among them we have identified more than 16 families with HNPCC; 4 showed absence of hMLH1, 1 showed absence of hMSH6, and 11 showed absence of hMSH2. All tumors that showed MSI also showed absence of either one of the three MMR proteins. We present the clinical, pathological and molecular features of our patients and discuss the implication of this data on future recommendations.
authors.affiliation: Sharret Institute of Oncology, Hadassah Hebrew University Medical Center. yaelg@hadassah.org.il
authors.forename: Yael
authors.initials: Y
authors.lastname: Goldberg
authors.forename: Rinnat
authors.initials: R
authors.lastname: Porat
authors.forename: Michal
authors.initials: M
authors.lastname: Sagi
authors.forename: Avital
authors.initials: A
authors.lastname: Eilat
authors.forename: Inbal
authors.initials: I
authors.lastname: Kedar
authors.forename: Chen
authors.initials: C
authors.lastname: Shochat
authors.forename: Suzan
authors.initials: S
authors.lastname: Mendelson
authors.forename: Tamar
authors.initials: T
authors.lastname: Hamburger
authors.forename: Aviram
authors.initials: A
authors.lastname: Nissan
authors.forename: Ayala
authors.initials: A
authors.lastname: Hubert
authors.forename: Stavit
authors.initials: S
authors.lastname: Shalev
authors.forename: Dani
authors.initials: D
authors.lastname: Bercovich
authors.forename: Eli
authors.initials: E
authors.lastname: Pikarski
authors.forename: Israela
authors.initials: I
authors.lastname: Lerer
authors.forename: Dvorah
authors.initials: D
authors.lastname: Abeliovich
authors.forename: Tamar
authors.initials: T
authors.lastname: Pretetz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D020137:Base Pair Mismatch; D002851:Chromatography, High Pressure Liquid; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005817:Genetic Counseling; D006757:Hospital Units; D006801:Humans; D008297:Male; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011336:Probability