title: Molecular genetics for clinical management of colorectal carcinoma. 17p, 18q, and 22q loss of heterozygosity and decreased DCC expression are correlated with the metastatic potential.
abstract: BACKGROUND
  The molecular genetic changes associated with colorectal carcinoma are among the best understood of any common human cancer. The genetic changes during the late stages of colorectal carcinomas may be useful in clinical management for determining the metastatic potential of the carcinoma.
  
  
  METHODS
  Tumor tissues were evaluated by restriction fragment length polymorphism (RFLP) analysis of chromosomes 5q, 17p, 18q, and 22q (n = 98), by reverse transcription-polymerase chain reaction (RT-PCR) analysis of messenger RNA expression of the DCC gene (deleted in colorectal carcinoma) (n = 27) and by immunohistochemical analysis of p53 protein expression (n = 44).
  
  
  RESULTS
  Loss of heterozygosity (LOH) on chromosomes 17p, 18q, and 22q, but not on 5q, was much more frequently detected in advanced carcinomas than in intramucosal carcinomas (P < 0.01). 17p LOH was significantly correlated with vascular invasion (P < 0.001), whereas 18q LOH was correlated with lymphatic invasion and hepatic metastasis (P < 0.01), and 22q LOH was correlated with lymph node metastasis (P < 0.05). LOH on 5q did not show a significant correlation with any factors of tumor invasion or metastasis. DCC expression was not observed in any of five hepatic metastasis or in five of seven advanced carcinomas that were accompanied by hepatic metastasis (10 of 12). However, a similar lack of expression was observed in only 5 of 15 carcinomas without hepatic metastasis (P < 0.05). p53 Expression was found to vary in both primary and metastatic carcinomas by immunohistochemistry.
  
  
  CONCLUSIONS
  The clinical application of molecular genetics (i.e., RFLP analysis of chromosome 17p, 18q, and 22q and RT-PCR analysis of DCC expression into messenger RNA) can be used to determine the metastatic potential of colorectal carcinomas.
authors.affiliation: Department of Pathology, Tokyo Metropolitan Komagome Hospital, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Iino
authors.forename: M
authors.initials: M
authors.lastname: Fukayama
authors.forename: Y
authors.initials: Y
authors.lastname: Maeda
authors.forename: M
authors.initials: M
authors.lastname: Koike
authors.forename: T
authors.initials: T
authors.lastname: Mori
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: R
authors.initials: R
authors.lastname: Kikuchi-Yanoshita
authors.forename: M
authors.initials: M
authors.lastname: Miyaki
authors.forename: S
authors.initials: S
authors.lastname: Mizuno
authors.forename: S
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002902:Chromosomes, Human, 16-18; D002904:Chromosomes, Human, 21-22 and Y; D002905:Chromosomes, Human, 4-5; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000556:secondary; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016163:Genes, DCC; D006579:Heterozygote; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53