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.
Soong
R
R
Department of Surgery, University of Western Australia, Nedlands.
Robbins
P D
PD
Dix
B R
BR
Grieu
F
F
Lim
B
B
Knowles
S
S
Williams
K E
KE
Turbett
G R
GR
House
A K
AK
Iacopetta
B J
BJ
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