Expression of p73 and its relation to histopathology and prognosis in hepatocellular carcinoma.
BACKGROUND
The protein p73, the first identified homologue of the tumor suppressor gene p53 (also known as TP53), has been shown to induce apoptosis (programmed cell death), but its function in tumor development has not been established. This study was undertaken to investigate the expression of p73 in liver tissue of patients with hepatocellular carcinoma (HCC) and to determine whether this expression has any impact on prognosis.


METHODS
In situ hybridization and immunohistochemistry for the detection of p73 RNA transcripts and protein, respectively, were performed in tissues from 193 patients with curatively (R0-) resected HCC. Patients receiving liver transplantation were excluded. The results obtained were analyzed with respect to their association with pathohistologic stage, Edmondson grade, p53 expression status and several histopathologic factors of possible prognostic value, and, finally, with patient survival.


RESULTS
RNA transcripts encoding p73 were detected by in situ hybridization in tumor cells but not in stromal, endothelial, or inflammatory cells or in cholangiocytes. Transcripts were also found occasionally in non-neoplastic hepatocytes. By immunohistochemistry, we detected p73 protein in 61 (32%) of the 193 carcinomas examined. Positive immunohistochemical staining was confined to the cell nucleus. Univariate survival analysis showed that p73 expression status was statistically significantly related to prognosis (two-sided P<.0001). Patients with p73-positive tumors had a poorer prognosis than those with p73-negative carcinomas. Multivariate Cox survival analysis identified the age of the patient, p73 expression status, co-existing cirrhosis, and Edmondson grade as independent prognostic factors.


CONCLUSIONS
The protein p73 is overexpressed by a subset of HCCs and could serve as a useful indicator of prognosis in patients with this disease.
Institute of Pathology, Department of Internal Medicine, University of Leipzig, Germany. tana@medizin.uni-leipzig.de
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A
Tannapfel
M
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Wasner
K
K
Krause
F
F
Geissler
A
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Katalinic
J
J
Hauss
J
J
Mössner
K
K
Engeland
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Wittekind
D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000473:pathology*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008113:Liver Neoplasms / Q000737:chemistry* / Q000473:pathology*; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis* / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D012189:Retrospective Studies; D016019:Survival Analysis; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D017931:DNA Primers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins