title: Appearance of epithelial and stromal genomic instability in background colorectal mucosa of sporadic colorectal cancer patients: relation to age and gender.
abstract: BACKGROUND
  We have previously demonstrated that not only epithelial but also stromal genetic instability possibly contributes to colorectal tumorigenesis. To assess the increasing risk of carcinogenesis in the colorectum with aging, we examined genomic instability in both epithelia and stroma in the background noncancerous mucosa of patients with colorectal carcinomas.
  
  
  METHODS
  In 213 noncancerous colorectal mucosa samples from colorectal cancer cases and 51 normal mucosa specimens of diverticulosis cases, epithelial and stromal genomic instability was analyzed with National Cancer Institute standard microsatellite markers, chromosome 17 (Chr.17) markers and tumor suppressor gene-related markers, using a combination of laser-capture microdissection and GeneScan approaches. Results were compared with immunohistochemically demonstrated expression of FHIT, Rb, WT1, hMLH1 and hMSH2.
  
  
  RESULTS
  Genomic instability (MSI and LOH) in both epithelia and stroma appeared after around 40 years of age and remained relatively constant thereafter at relatively low frequencies (4.8-30.4%). The Epithelial LOH tended to show a stepwise increase in people in their 40s and 50s along with aging, especially in males. Overall frequencies of both epithelial MSI and LOH in left-side colon and LOH in right-side colon were significantly higher in males than in females. Epithelial hMLH1 expression in MSI (-) cases tended to be reduced with aging.
  
  
  CONCLUSIONS
  Genomic instability of both MSI and LOH in noncancerous colonic mucosa, and more particularly epithelial and stromal LOH, appears relatively early in adults, suggesting age-related changes which increase the risk of cancer development, particularly in males.
authors: Department of Cellular and Histo-pathology, Kitasato University Postgraduate School of Medical Sciences, Sagamihara, Japan.
authors: Harue
authors: H
authors: Umeto
authors: Tsutomu
authors: T
authors: Yoshida
authors: Kayo
authors: K
authors: Araki
authors: Hiroko
authors: H
authors: Yagishita
authors: Tetuo
authors: T
authors: Mikami
authors: Isao
authors: I
authors: Okayasu
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D043963:Diverticulosis, Colonic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D008875:Middle Aged; D012737:Sex Factors; D017154:Stromal Cells / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor