Concordance between p53 protein overexpression and gene mutation in a large series of common human carcinomas.
Immunohistochemical (IHC) detection of p53 protein was compared with the presence of p53 gene mutation in many colorectal (n = 100), breast (n = 92), endometrial (n = 122), and gastric (n = 116) carcinomas. Two commercially available antibodies, DO7 and CM1, were used for IHC analysis of paraffin-embedded tissue sections. Screening for gene mutations in frozen and paraffin-embedded tumor samples was carried out using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP). The frequency of nuclear staining with DO7 or CM1 for each tumor type, respectively, was colorectal (36%, 23%); breast (15%, 19%); endometrial (21%, 33%); and gastric (23%,-). Overall correlation between the two antibodies for nuclear staining was 90% for the 314 tumors analyzed. Cytoplasmic staining was observed with DO7 in 7% of breast and 5% of gastric carcinomas and with CM1 in 17% of breast and 54% of endometrial carcinomas. p53 gene mutation was found in 39% of colorectal, 28% of breast, 13% of endometrial, and 25% of gastric cancers. The concordance between p53 nuclear overexpression and gene mutation (both positive or both negative) was 68% for colorectal, 79% for breast, 76% for endometrial, and 73% for gastric carcinomas. This study provides further evidence that IHC detection of p53 protein accumulation does not always indicate the presence of a gene mutation and vice versa. Discordant results were observed in approximately 20% to 30% of the tumors studied, highlighting the need for careful characterization of both p53 gene and protein alterations when assessing the relationship between p53 status and tumor behavior.
Department of Surgery, University of Western Australia, Nedlands.
R
R
Soong
P D
PD
Robbins
B R
BR
Dix
F
F
Grieu
B
B
Lim
S
S
Knowles
K E
KE
Williams
G R
GR
Turbett
A K
AK
House
B J
BJ
Iacopetta
D001943:Breast Neoplasms / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015810:Linkage Disequilibrium; D009154:Mutation; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D013274:Stomach Neoplasms / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics*
D016159:Tumor Suppressor Protein p53