Prognostic significance of p53 abnormalities in colorectal carcinoma detected by PCR-SSCP and immunohistochemical analysis.
Abnormalities in the p53 tumour suppressor gene and in the expression of its protein are common in colorectal carcinoma. The prognostic significance of these p53 abnormalities was studied in 66 patients with colorectal cancer, followed for more than 10 years. Single-strand conformation polymorphism (SSCP) analysis was used to detect alterations in exons 5-8 of the p53 gene. Paraffin sections were examined immunohistochemically for p53 overexpression with the monoclonal antibody DO-7 (Dako) both with and without microwave antigen retrieval. Abnormalities of the p53 gene were found in 41 per cent of cases by SSCP analysis. Outcome was unrelated to SSCP abnormalities (P = 0.19), except for the Dukes' A and B subgroup, where decreased survival was found in cases with abnormal SSCP (P = 0.01). Overexpression of p53 protein was seen by immunohistochemistry in 47 per cent of cases without, and in 52 per cent of cases with microwave antigen retrieval. Immunohistochemical overexpression of p53 protein either with or without microwave antigen retrieval was an independent prognostic indicator of poor survival. These results suggest that for routine purposes, immunohistochemical detection of the p53 protein product may be more useful than SSCP analysis of the encoding p53 gene in identifying those at high risk of colorectal cancer recurrence and death.
Leahy
D T
DT
Department of Pathology and Gastroenterology, St. Vincent's Hospital, University College, Dublin, Ireland.
Salman
R
R
Mulcahy
H
H
Sheahan
K
K
O'Donoghue
D P
DP
Parfrey
N A
NA
D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D016158:Genes, p53; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53