Correlation between DNA content and p53 deletion in colorectal cancer.

OBJECTIVE: To find out whether tumour DNA content correlates with allelic loss of p53 and other pathological features in primary colorectal carcinomas. DESIGN: Ongoing prospective study. SETTING: University hospital, Italy. SUBJECTS: 128 patients who had undergone radical resections for colorectal carcinoma. INTERVENTIONS: Flow cytometric measurement of tumour DNA content and detection of allelic loss on the short arm of chromosome 17 by Southern blot (restriction fragment length polymorphism) analysis in fresh tumour specimens. MAIN OUTCOME MEASURES: Correlation between DNA ploidy and deletion of p53, as well as between these two genetic events and clinicopathological variables. RESULTS: Interpretable DNA histograms were obtained for 122 tumour specimens. Forty-three tumours (35%) were diploid and 79 (65%) aneuploid. The diploid tumours were significantly more common in the proximal colon (from the caecum to the splenic flexure) than in the distal colon (from the descending colon to the rectum) (p = 0.002). The allelic state on the short arm of chromosome 17 was evaluated in 80 heterozygous patients. Forty-four tumour specimens (55%) showed deletion of 17p. Allelic loss of p53 was significantly more common in the distal and rectal tumours than in the proximal ones (p < 0.0001). Aneuploidy was more common among those tumours which had shown deletion of p53 than in those that had not (p = 0.0008). CONCLUSIONS: DNA aneuploidy was significantly associated with the deletion of the p53 gene. This suggests that the functional loss of p53 may favour the growth and establishment of an aneuploid cell population within tumours. Tumours of the proximal and distal colon differ in their genetic nature.

Colonic cell proliferation in normal mucosa of patients with colon cancer.

Cell kinetics parameters have been analysed in colonic mucosa at different distances from a tumour in patients with colon carcinoma. Total cell number (TCN), 3H thymidine labelling index (TLI), mitotic index (MI), Goblet cell index (GCI) and the distribution of labelled cells along the crypt column (cell position frequency plot) were determined in well-aligned crypts. Total cell number, GCI and the labelled cell position frequency plots were similar in different samples from the same individual. A negative linear correlation between TCN and TLI was observed. The analysis of the cell position plots showed two patterns 1) with a high concentration in the bottom fifth of the crypt and 2) with frequent labelled cells at high positions. Whereas a negative correlation between overall TLI and the percent contribution to the TLI of the lowermost fifth was seen, the correlation was positive for the next 3 fifths and labelling was absent in the last part of the crypt.