Expression of p73 and Its relation to histopathology and prognosis in hepatocellular carcinoma

Background: The protein p73, the first identified homologue of the tumor su ppressor 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 p7 3 in liver tissue of patients with hepatocellular carcinoma (HCC) and to de termine whether this expression has any impact on prognosis. Methods: In si tu hybridization and immunohistochemistry for the detection of p73 RNA tran scripts and protein, respectively, were performed in tissues from 193 patie nts with curatively (R0-) resected HCC. Patients receiving liver transplant ation were excluded. The results obtained were analyzed with respect to the ir association with pathohistologic stage, Edmondson grade, p53 expression status and several histopathologic factors of possible prognostic value, an d, finally, with patient survival. Results: RNA transcripts encoding p73 we re detected by in situ. hybridization in tumor cells but not in stromal, en dothelial, or inflammatory cells or in cholangiocytes. Transcripts mere als o found occasionally in non-neoplastic hepatocytes. Ey immunohistochemistry , we detected p73 protein in 61 (32%) of the 193 carcinomas examined. Posit ive immunohistochemical staining was confined to the cell nucleus, Univaria te survival analysis showed that p73 expression status was statistically si gnificantly related to prognosis (two-sided P<.0001), Patients with p73-pos itive 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 independe nt prognostic factors. Conclusion: The protein p73 is overexpressed by a su bset of HCCs and could serve as a useful indicator of prognosis in patients with this disease.