p53 expression and DNA ploidy pattern in Egyptian colorectal carcinoma

BACKGROUND/AIMS: p53 gene mutation occurs in about 50-60% of colorectal carcinoma cases. This mostly occurs as a late event in the adenoma-carcinoma sequence. These late stages are associated with more aneuploidy compared to adenomas and early carcinomas. However there is a controversy regarding the relation between p53 overexpression and DNA index. This study was designed to investigate the relationship between p53 status and DNA ploidy pattern. METHODOLOGY: Nuclear DNA content of paraffin-embedded material from 83 colectomy specimens for colorectal carcinoma was measured by flow cytometry. Also, p53 was detected by immunohistochemistry in 73 out of the 83 tumor cases using a monoclonal antibody that detects both wild and mutant p53 proteins (Biogenex 1801). RESULTS: Aneuploidy was identified in 37 cases (46.25%). Tumors with rectal location were significantly more aneuploid in comparison to other sites (P = 0.009), p53 staining showed three patterns: diffuse staining (29 cases), focal (13 cases), and negative (31 cases). Diffuse p53 staining was associated with aneuploidy (P = 0.04). The majority of DNA indices fell within the range 1.1-2.2 (32 out of 37). Twenty-one of these had DNA index = 1.1-1.8 (aneuploidy short of tetraploidy) significantly associated with diffuse p53 staining compared with peritetraploid cases (DNA index 1.8-2.2) (P = 0.034). CONCLUSIONS: p53 immunohistochemistry demonstrates two distinct patterns in colorectal carcinoma. Diffuse p53 staining, which is associated with aneuploidy short of tetraploidy (DNA index 1.1-1.8), a finding which is different from previously published work. Focal p53 staining pattern, in contrast, is related to high G2M and more abnormal tetraploid peaks but less aneuploidy.