TY - JOUR
T1 - p53 protein accumulation and mutations in normal and benign breast tissue
AU - Kandel, Rita
AU - Li, Shu Qiu
AU - Ozcelik, Hilmi
AU - Rohan, Tom
PY - 2000
Y1 - 2000
N2 - Mutations in the p53 gene are amongst the most common molecular changes detected in breast cancer, and there are several reports suggesting that changes in p53 may contribute to the pathogenesis of this disease. In a previous case-control study, we demonstrated that p53 protein accumulation detected by immunohistochemistry in normal or benign breast tissue was associated with a 2.54-fold increase in the risk of subsequent breast cancer. In this study, we investigated whether p53 gene mutations were present in the 29 p53 immunopositive normal or benign breast tissue samples and in 15 p53 immunonegative normal or benign breast tissue samples selected randomly from the original study. DNA was extracted from paraffin sections and underwent PCR-SSCP analysis for exons 4 to 10. PCR products that showed abnormal mobility were excised and sequenced. Sixteen (59.2%) of the 27 immunopositive breast tissue samples and 4 (26.7%) of the 15 immunonegative samples had p53 sequence changes. There was no obvious association between the occurrence of these alterations and any specific histopathologic features. Ten cases showed p53 mutations, and they were all missense base substitutions of the transition type. Thirteen other gene changes occurred in II breast tissue samples and consisted of 8 silent (no amino acid change), 4 intronic alterations, and I indeterminate alteration. One individual had both a mutation and a silent change. In summary, p53 gene alterations can occur in normal or benign breast tissue, but resolution of their role in the pathogenesis of breast cancer will require long-term follow-up studies involving comparisons of breast cancer occurrence in patients with and without p53 mutations as well as functional assays to determine their significance. (C) 2000 Wiley-Liss, Inc.
AB - Mutations in the p53 gene are amongst the most common molecular changes detected in breast cancer, and there are several reports suggesting that changes in p53 may contribute to the pathogenesis of this disease. In a previous case-control study, we demonstrated that p53 protein accumulation detected by immunohistochemistry in normal or benign breast tissue was associated with a 2.54-fold increase in the risk of subsequent breast cancer. In this study, we investigated whether p53 gene mutations were present in the 29 p53 immunopositive normal or benign breast tissue samples and in 15 p53 immunonegative normal or benign breast tissue samples selected randomly from the original study. DNA was extracted from paraffin sections and underwent PCR-SSCP analysis for exons 4 to 10. PCR products that showed abnormal mobility were excised and sequenced. Sixteen (59.2%) of the 27 immunopositive breast tissue samples and 4 (26.7%) of the 15 immunonegative samples had p53 sequence changes. There was no obvious association between the occurrence of these alterations and any specific histopathologic features. Ten cases showed p53 mutations, and they were all missense base substitutions of the transition type. Thirteen other gene changes occurred in II breast tissue samples and consisted of 8 silent (no amino acid change), 4 intronic alterations, and I indeterminate alteration. One individual had both a mutation and a silent change. In summary, p53 gene alterations can occur in normal or benign breast tissue, but resolution of their role in the pathogenesis of breast cancer will require long-term follow-up studies involving comparisons of breast cancer occurrence in patients with and without p53 mutations as well as functional assays to determine their significance. (C) 2000 Wiley-Liss, Inc.
UR - http://www.scopus.com/inward/record.url?scp=0034079977&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034079977&partnerID=8YFLogxK
U2 - 10.1002/1097-0215(20000701)87:1<73::AID-IJC11>3.0.CO;2-U
DO - 10.1002/1097-0215(20000701)87:1<73::AID-IJC11>3.0.CO;2-U
M3 - Article
C2 - 10861455
AN - SCOPUS:0034079977
SN - 0020-7136
VL - 87
SP - 73
EP - 78
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 1
ER -