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GENOMIC INSTABILITY IN COLORECTAL CARCINOMAS: COMPARISON OF DIFFERENT EVALUATION METHODS AND THEIR BIOLOGICAL SIGNIFICANCE
Author(s) -
BOCKER TINA,
SCHLEGEL JÜRGEN,
KULLMANN FRANK,
STUMM GABRIELE,
ZIRNGIBL HUBERT,
EPPLEN JÖRG T.,
RÜSCHOFF JOSEF
Publication year - 1996
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(199605)179:1<15::aid-path553>3.0.co;2-n
Subject(s) - microsatellite instability , microsatellite , polymerase chain reaction , biology , oligomer restriction , immunohistochemistry , flow cytometry , pathology , genome instability , oligonucleotide , microbiology and biotechnology , colorectal cancer , genomic dna , ploidy , cancer research , dna , gene , genetics , cancer , dna damage , medicine , immunology , allele
In order to demonstrate the relationship between microsatellite instability and other types of genomic instability, a series of 56 sporadic colorectal carcinomas was investigated by flow cytometrical ploidy analysis, oligonucleotide fingerprinting, and microsatellite polymerase chain reaction (PCR). Stabilization of the p53 gene product was analysed by immunohistochemistry and proliferative activity was determined flow cytometrically and by silver staining of nucleolar organizer regions (AgNORs). Of the 56 carcinomas, 11 (19 per cent) exhibited microsatellite instability; 33 of the cases were aneuploid (59 per cent) and 29 (52 per cent) showed alterations of the oligonucleotide fingerprints. There was a significant correlation of microsatellite instability with localization of these tumours proximal to the splenic flexure, diploid DNA content, and less frequent p53 stabilization. A solid growth pattern, mucinous differentiation, and a Crohn's‐like lymphoid infiltrate were also characteristic for those tumours. The results demonstrate for the first time a significantly lower proliferative activity in tumours with microsatellite instability. Data obtained from DNA flow cytometry or from oligonucleotide fingerprinting did not correlate with such tumour characteristics. It is proposed that the use of microsatellite PCR facilitates specifically the detection of a group of colorectal cancers which may differ in pathogenesis and perhaps prognosis.