Nuclear accumulation of p53 protein correlates with mutations in the p53 gene on archival paraffin-embedded tissues of human breast cancer.
Fifty invasive ductal carcinomas of the breast were analyzed by immunohistochemistry, polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and direct sequencing after microdissection of conventional formalin-fixed, paraffin-embedded tissues. A highly significant association between the presence of p53 gene mutation and nuclear accumulation of p53 protein was found (P < 0.0001). Of 13 tumors that demonstrated p53 gene mutations, 11 (84.6%) showed nuclear accumulation of p53 protein. However, of 37 tumors in which gene mutations were not detected, only 5 (13.5%) showed nuclear accumulation of p53 protein. There was a statistically significant association between the nuclear accumulation of p53 protein and a higher histological grade (P < 0.001) or mitotic index (P < 0.01). In addition, gene mutations had a statistically significant association with a higher histological grade (P < 0.05) or mitotic index (P < 0.0001). Therefore, p53 abnormalities might be associated with an aggressive phenotype in breast cancer. We conclude that the immunohistochemical detection of nuclear p53 protein accumulation is highly associated with p53 gene mutations in archival paraffin-embedded tissues, and that this method is useful for rapid screening of p53 abnormalities.
Umekita
Y
Y
Department of Pathology, Faculty of Medicine, Kagoshima University.
Kobayashi
K
K
Saheki
T
T
Yoshida
H
H
D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism*; D005260:Female; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008940:Mitotic Index; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D009838:Oligodeoxyribonucleotides; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011960:Receptors, Estrogen / Q000032:analysis; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism*
D009838:Oligodeoxyribonucleotides; D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53