Growth dysregulation and p53 accumulation in human primary colorectal cancer

p53 accumulation is common in colorectal cancer, but effects on growth home ostasis are unclear. In this study, DNA content, cell cycle phase fractions and DNA strand-breaks consistent with apoptosis were assessed by flow cyto metry in 42 fresh primary colorectal tumours and matched normal mucosa. p53 accumulation was assessed in 37 fixed tumour sections, by immunohistochemi stry. In normal mucosa, 10.3 +/- 6.6% (mean +/- s.d.) cells were in DNA syn thesis phase while 28.7 +/- 17.9% showed apoptosis. A relationship suggesti ve of growth homeostasis, was observed between these parameters (r = 0.8; P < 0.05). In cancers, a greater number of cells were in DNA synthesis phase (15.6 +/- 12.9% tumour vs mucosa 10.3 +/- 6.6%; P < 0.02) while fewer show ed apoptosis than normal mucosa (18.5 +/- 17.0% tumour vs mucosa 28.7 +/- 1 7.9%; P < 0.01). DNA synthesis and apoptosis fractions were unrelated in ca ncers, suggesting growth dysequilibrium, p53 accumulation was detected in 5 9% (22/37) tumours and was associated with reduced apoptosis compared to p5 3-negative tumours or mucosa (14.8 +/- 15% p53 accumulation vs 26.3 +/- 18% p53-negative; P < 0.05; vs 28.7 +/- 17.9% mucosa; P < 0.05). p53 accumulat ion was unrelated to DNA synthesis phase fractions. p53 accumulation is acc ompanied by reduced apoptosis which may accentuate growth dysequilibrium in colorectal cancer.