Survivin overexpression in hepatocellular carcinoma is associated with p53 dysregulation.
BACKGROUND
Survivin is a recently described anti-apoptotic protein that is suppressed by wild-type p53 and is overexpressed in 41-70% of hepatocellular carcinomas from Asia. Two alternatively spliced transcripts have also been described: anti-apoptotic survivin-DeltaEx3 and non-anti-apoptotic survivin-2B. Survivin splice variant expression has not been studied in HCC, and little is known about survivin expression in hepatocellular carcinomas arising in other parts of the world, where risk factors are often different than they are in Asia.


OBJECTIVE
We studied survivin mRNA and protein expression in a United States cohort of hepatocellular carcinomas and correlated the findings with p53 immunopositivity.


METHODS
RT-PCR was performed for survivin, survivin-2B, and survivin-DeltaEx3 in 20 HCCs and one intrahepatic cholangiocarcinoma. Expression levels of total survivin were evaluated with real-time PCR. Protein expression was examined by immunohistochemistry.


RESULTS
Survivin was the major transcript, and all transcripts were present in all normal and neoplastic tissues; 11/20 (55%) HCCs and the one cholangiocarcinoma showed twofold or greater overexpression of survivin. Next, we examined survivin and p53 protein expression by immunohistochemistry on a separate series of 79 HCC, 13 fibrolamellar carcinomas, and 15 hepatic adenomas; 14/79 (17%) HCC, but none of the fibrolamellar carcinomas or hepatic adenomas, showed survivin protein overexpression, and 25/79 HCC (32%) showed abnormal nuclear accumulation of p53, which correlated with increased survivin expression.


CONCLUSIONS
All three survivin transcripts are present in normal liver and HCC. Survivin is the dominant transcript in HCC and is overexpressed in 55% of cases. Survivin protein overexpression is associated with aberrant p53 nuclear positivity.
Kannangai
Rajesh
R
Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21218, USA.
Wang
Jianzhou
J
Liu
Qiong Z
QZ
Sahin
Fikret
F
Torbenson
Michael
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000503:physiopathology; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D016158:Genes, p53 / Q000502:physiology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008113:Liver Neoplasms / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D009363:Neoplasm Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D000077022:Survivin
D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D015415:Biomarkers; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000077022:Survivin
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