WAF1 expression and p53 mutations in human colorectal cancers.

The expression of the WAF1 gene was examined in the tissues of primary colorectal cancers and of adjacent non-neoplastic mucosas by Western blot analysis. p53 mutations of these cancer tissues were also analyzed by the polymerase chain reaction/single-strand conformation polymorphism followed by direct sequencing. Missense mutations of p53 were recognized in 19 out of 40 cases. Five cancers (12.5%) displayed much lower expression of WAF1 than did their corresponding mucosas, and all of them contained mutant p53. Fourteen cancers (35%) expressed the same level of WAF1 as their mucosas, and 5 of them had mutant p53. Twenty-one cancers (52.5%) had much higher WAF1 expression than their mucosas, and 9 of them had mutant p53. When Duke's classification was applied to these colorectal cancers, it was found that the cancers with reduced expression of WAF1 basically coincided with late (C or D) stages (4 out of 5 cases), while the cancers with higher WAF1 expression were consistent with early (A or B) stages (17 out of 21 cases). Down-regulation of WAF1 in colorectal cancer tissues may be implicated in tumor progression.