title: Early-onset colorectal cancer patients without family history are "at very low risk" for lynch syndrome.
abstract: BACKGROUND
  Several studies evaluated the prevalence of Lynch Syndrome (LS) in young onset colorectal cancer (CRC) patients and the results were extremely variable (5%-20%). Immunohistochemistry (IHC) for MMR proteins and/or MSI analysis are screening tests that are done, either by themselves or in conjunction, on colon cancer tissue to identify individuals at risk for LS. The primary aim of our study was to evaluate the prevalence of LS in a large series of early-onset CRC without family history compared with those with family history. The secondary aim was to assess the diagnostic accuracy of IHC and MSI analysis as pre-screening tools for LS.
  
  
  METHODS
  Early-onset CRC patients (≤ 50 years) were prospectively recruited in the study. IHC and MSI analysis were performed in all the patients. Germ-line mutation analysis (GMA) was carried out in all MMR deficient tumors. A logistic regression model was performed to identify clinical features predictive of MSI-H.
  
  
  RESULTS
  117 early onset CRC cases were categorized in three groups (A, B, C) according with family history of CRC. IHC and MSI analysis showed MMR deficiency in 6/70 patients (8.6%) of group A, 24/40 patients (60%) of group B and none of group C. GMA showed a deleterious mutation in 19 (47.5%) patients of group B. MSI analysis had a diagnostic accuracy of 95.7% (CI 92.1-99.4) and IHC of 83.8% (CI 77.1-90.4). The logistic regression model revealed that by using a combination of the two features "No Amsterdam Criteria" and "left sided CRC" to exclude MSI-H, accuracy was 89.7% (84.2-95.2).
  
  
  CONCLUSIONS
  Early-onset CRC patients, with left sided CRC and without family history are "at very low risk" for Lynch syndrome. The two simple criteria of family history and CRC site could be used as a pre-screening tool to evaluate whether or not patients should undergo tissue molecular screening. In the few cases of suspected LS (right sided CRC and/or Amsterdam Criteria), a reasonable approach could be to perform MSI analysis first and IHC afterwards only in MSI-H patients.
authors.affiliation: Division of Gastroenterology and Digestive Endoscopy, Regina Elena National Cancer Institute, IFO Via Elio Chianesi 53, 00144 Rome, Italy. stigliano@ifo.it.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Stigliano
authors.forename: Lupe
authors.initials: L
authors.lastname: Sanchez-Mete
authors.forename: Aline
authors.initials: A
authors.lastname: Martayan
authors.forename: Maria
authors.initials: M
authors.lastname: Diodoro
authors.forename: Beatrice
authors.initials: B
authors.lastname: Casini
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.forename: Marcello
authors.initials: M
authors.lastname: Anti
mesh_terms: D000328:Adult; D017668:Age of Onset; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000378:metabolism; D053843:DNA Mismatch Repair; D004252:DNA Mutational Analysis; D045643:DNA Repair Enzymes / Q000235:genetics; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D011446:Prospective Studies; D012372:ROC Curve; D012306:Risk; D055815:Young Adult
chemical_list: D045643:DNA Repair Enzymes