Prognostic significance of p53 expression, chromosome 17 copy number, and DNA ploidy in non-metastasized colorectal carcinomas (stages IB and II).
METHODS
Paraffin-embedded tumor tissue from 101 non-metastasized colorectal adenocarcinomas (tumor stages IB and II--that is, pT2 and 3, pN0, M0) was investigated for p53 expression by immunohistology (IH) (moab DO1), chromosome 17 (#17) copy number by interphase cytogenetics using non-radioactive in situ hybridization (NISH) with a centromer-specific DNA probe (D17Z1), and DNA ploidy by flow cytometry (FCM). The aims of the study were 1) to test whether numerical #17 aberrations are involved in functional TP53 loss in locally confined colorectal carcinomas; 2) to search for correlations between aberrant p53 expression and #17 aberrations with DNA ploidy and histopathology; and 3) to test the prognostic significance of these factors.


RESULTS
Sixty cases (59.4%) showed nuclear p53 expression IH (low-grade p53 accumulation (< 50%), n = 16 (15.8%); high-grade (> or = 50%), n = 44 (43.6%)). Nish showed #17 aneusomy in 46% of the carcinomas (34% deletions, 12% gains). In FCM analysis, 43% of the carcinomas were DNA non-diploid. p53 overexpression correlated statistically significantly with FCM non-diploidy (p = 0.013). Furthermore, #17 aneusomy also correlated with FCM non-diploidy (p = 0.001). However, there was no association between #17 status and p53 expression (IH).


CONCLUSIONS
Our data suggest a role for the TP53 gene in the aneuploidization process. Numerical deletions of #17, however, were not associated with p53 immunoreactivity in the analyzed tumors. With regard to prognosis, the most important independent variable in stage IB/II colorectal carcinomas was tumor stage, followed by high-grade p53 expression of tumor cells; #17 aneusomy was an independent risk factor for tumor relapse/progression but not for survival. As alterations of the investigated variables were not found in all carcinomas under study, different pathogenetic pathways seem to exist in colorectal carcinogenesis.
Baretton
G B
GB
Institute of Pathology, University of Munich, Germany.
Vogt
M
M
Müller
C
C
Diebold
J
J
Schneiderbanger
K
K
Schmidt
M
M
Löhrs
U
U
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D000782:Aneuploidy; D002886:Chromosomes, Human, Pair 17; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics*; D004171:Diploidy; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53