Correlation of mutation and immunohistochemistry of p53 in hepatocellular carcinomas in Korean people.
The degree of correlation between sequencing and immunohistochemisty (IHC) for detecting mutations of p53 has not been well established in human hepatocellular carcinoma (HCC). We analyzed 36 HCCs from Korean people for p53 mutation at exons 4-10 by PCR-SSCP and sequencing, and compared the results with the IHC positivity. p53 mutations were identified in 7 out of 36 HCCs (19.4%). These mutations were found widely throughout exons 4-8. No mutation was detected in codon 249. Among the 7 mutations, 6 missense mutations were detected in 15 HCCs with > or =5% immunoreactive tumor cells and one nonsense mutation was in 21 HCCs with <5% immunoreactive tumor cells. The sensitivity for p53 mutation was 85.7% (6/7), the specificity 69.0% (20/29), the predictive value of positive IHC 40.0% (6/15), and the predictive value of negative IHC 95.2% (20/21). Two missense mutations were detected in 25 cases with <10% immunoreactive tumor cells. Predictive values of both positive IHC and negative IHC were higher in > or =5% overexpression group than in > or =10% overexpression group or >0% overexpression group. This study suggests that 5% immunoreactivity is a reliable immunohistochemical threshold value to detect p53 mutations in HCCs and the spectrum of p53 mutations in HCCs in Korean people is different from that of high aflatoxin B1 exposure areas.
Lee
Shi Nae
SN
Department of Pathology, Ewha Womans University College of Medicine, Seoul, Korea.
Park
Cheol Keun
CK
Sung
Chang Ohk
CO
Choi
Jong Sun
JS
Oh
Young Lyun
YL
Cho
Jae Won
JW
Yoo
Byung Chul
BC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism*; D005091:Exons; D005260:Female; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D007723:Korea; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D016159:Tumor Suppressor Protein p53