Manuel Guix1,2, Anna Colomer1, Nadina Erill1, M. Assumpció Cañadas2, Ruth Román1, Xavier Puig1,2, Carlos Cordón-Cardó3.
1BIOPAT, Grup Assistència, Barcelona; 2HISTOPAT Laboratoris, Barcelona; 3Division of Molecular Pathology, Memorial Sloan-Kettering Cancer Center, New York.
Multiple studies using primary tumors have reported that alterations in p53 expression and detection of TP53 mutations are associated with clinical aggressiveness and poor response to specific therapies. However, there is no general agreement regarding the optimal technical approach to the analysis of p53. We have studied 100 primary colorectal adenocarcinomas (CRA) by IHC (PAb 1801) and PCR-SSCP (exons 4-8) followed by direct sequencing of shifted bands. p53 nuclear staining was undetectable (score “0”) in 29 (29%) of the cases. However, gene mutations were detected in 15 of these cases, all of them leading to abnormal proteins. IHC was scored as <10% tumor cells positive in 15 (15%) of the cases (still “negative,” since the cut-off value for positivity was 10% – see below). Nevertheless, TP53 gene mutations were only detected in 2 of these cases. p53 nuclear immunoreactivities were observed in 56 (56%) of the cases (scored as >10% tumor cells positive), of which TP53 gene mutations were identified in 51 cases. These results reveal that IHC assessment does not predict TP53 mutation status in CRA, mainly in cases displaying absence of nuclear staining.