Prognostic significance of p53 expression, chromosome 17 copy number, and DNA ploidy in non-metastasized colorectal carcinomas (Stages IB and II)

Background and Methods: Paraffin-embedded tumor tissue from 101 non-metastasized colorectal adenocarcinomas (tumor stages IB and II-that is, pT2 and 3, pNO, MO) was investigated for p53 expression by immunohistology (TH) (moab D01), 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 in IH (low-grade p53 accumulation (<50%), n = 16 (15.8%); high-grade (greater than or equal to 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.