title: Left-sided early-onset vs late-onset colorectal carcinoma: histologic, clinical, and molecular differences.
abstract: OBJECTIVE
  Carcinomas of the left colon represent a neoplasm of older patients (late onset), but epidemiologic evidence has been showing an increasing incidence in patients 50 years or younger (early onset). In this study, we investigate pathologic and molecular features of early- and late-onset carcinoma of the left colon.
  
  
  METHODS
  We selected 22 patients 50 years or younger and 21 patients 70 years or older with left-sided colorectal carcinoma (CRC). All samples were evaluated for pathologic features, microsatellite instability, and KRAS and BRAF mutations. Moreover, both groups were analyzed to identify CpG island methylator phenotype features and assessed with restriction landmark genome scanning (RLGS) to unveil differential DNA methylation patterns.
  
  
  RESULTS
  Early-onset patients had advanced pathologic stages compared with late-onset patients (P = .0482). All cases showed a microsatellite stable profile and BRAF wild-type sequence. Early-onset patients (43%) more frequently had mutations at KRAS codon 12 compared with late-onset patients (14%) (P =.0413). RLGS showed that patients younger than 50 years who had CRC had a significantly lower percentage of methylated loci than did patients 70 years or older (P = .04124), and differential methylation of several genomic loci was observed in the two groups.
  
  
  CONCLUSIONS
  Our results suggest that left-sided CRCs may present differential patterns of aberrant DNA methylation when they are separated by age.
authors.affiliation: From the Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, University of Rome "La Sapienza," Rome, Italy; emanuela.pilozzi@uniroma1.it.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Pilozzi
authors.affiliation: Department of Cellular Biotechnologies and Hematology, University of Rome "La Sapienza", Rome, Italy;
authors.forename: Carmen
authors.initials: C
authors.lastname: Maresca
authors.affiliation: From the Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, University of Rome "La Sapienza," Rome, Italy;
authors.forename: Enrico
authors.initials: E
authors.lastname: Duranti
authors.affiliation: Surgical Pathology Unit "San Giovanni Calibita" Fatebenefratelli Hospital, Rome, Italy; and.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Giustiniani
authors.affiliation: Department of Cellular Biotechnologies and Hematology, University of Rome "La Sapienza", Rome, Italy;
authors.forename: Caterina
authors.initials: C
authors.lastname: Catalanotto
authors.affiliation: Department of Cellular Biotechnologies and Hematology, University of Rome "La Sapienza", Rome, Italy;
authors.forename: Marco
authors.initials: M
authors.lastname: Lucarelli
authors.affiliation: Department of Cellular Biotechnologies and Hematology, University of Rome "La Sapienza", Rome, Italy;
authors.forename: Carlo
authors.initials: C
authors.lastname: Cogoni
authors.affiliation: Department of Medical-Surgical Sciences and Translation Medicine, Sant'Andrea Hospital, University of Rome "La Sapienza," Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Ferri
authors.affiliation: From the Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, University of Rome "La Sapienza," Rome, Italy;
authors.forename: Luigi
authors.initials: L
authors.lastname: Ruco
authors.affiliation: Department of Cellular Biotechnologies and Hematology, University of Rome "La Sapienza", Rome, Italy;
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zardo
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D004502:Education, Medical, Continuing; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: BRAF; DNA methylation; Early-onset colorectal carcinoma; KRAS; MSI