title: Chromosome 5q loss in colorectal flat adenomas.
abstract: OBJECTIVE
  Flat adenomas are a subgroup of colorectal adenomas that have been associated with a more aggressive clinical behavior compared with their polypoid counterparts. Here, we aimed to compare one of the molecular changes most explicitly associated with adenoma to carcinoma progression, that is, chromosomal instability, between flat and polypoid colorectal adenomas.
  
  
  METHODS
  Consecutive series of 83 flat and 35 polypoid adenomas were analyzed for DNA copy number changes using a high-resolution array comparative genomic hybridization platform, microsatellite instability (MSI) status, and for mutations in the adenomatous polyposis coli (APC) gene. Immunohistochemical stainings for CD3, CD8, and FoxP3 expression were carried out.
  
  
  RESULTS
  Patterns of DNA copy number changes differed between the two phenotypes, with significantly more frequent loss of 5q14.3 and 5q15-q31.1 in flat adenomas, whereas losses of 1p36.32-p35.3, 10q25.3, 17p12, and chromosome 18 were more frequent in polypoid adenomas (false discovery rate < 0.2). MSI was observed in one flat adenoma. As the 5q15-q31.1 region harbors the APC locus, APC mutation status was investigated, showing significantly less mutations in flat adenomas (P = 0.04). An initial exploration of a possible association of 5q loss with inflammation indicated that tumor-infiltrating lymphocytes were more abundant in the stroma of flat adenomas compared with that of polypoid adenomas.
  
  
  CONCLUSIONS
  Flat and polypoid adenomas have partially distinct chromosomal profiles, consistent with differences in the biology underlying these phenotypes. Alterations more specific to flat adenomas, in particular 5q loss, may be associated with inflammation.
authors: Departments of Pathology, Epidemiology and Biostatistics, Gynaecology, and Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Quirinus J M
authors: QJ
authors: Voorham
authors: Beatriz
authors: B
authors: Carvalho
authors: Angela J
authors: AJ
authors: Spiertz
authors: Nicole C T
authors: NC
authors: van Grieken
authors: Sandra
authors: S
authors: Mongera
authors: Eveline J A
authors: EJ
authors: Rondagh
authors: Mark A
authors: MA
authors: van de Wiel
authors: Ekaterina S
authors: ES
authors: Jordanova
authors: Bauke
authors: B
authors: Ylstra
authors: Martin
authors: M
authors: Kliment
authors: Heike
authors: H
authors: Grabsch
authors: Bjorn J
authors: BJ
authors: Rembacken
authors: Tomio
authors: T
authors: Arai
authors: Adriaan P
authors: AP
authors: de Bruïne
authors: Silvia
authors: S
authors: Sanduleanu
authors: Philip
authors: P
authors: Quirke
authors: Chris J J
authors: CJ
authors: Mulder
authors: Manon
authors: M
authors: van Engeland
authors: Gerrit A
authors: GA
authors: Meijer
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein