Diagnostic and Prognostic Aspects of Hepatocellular Carcinoma – A Retrospective Analysis in 145 Patients

Holger G. Hass, Claudio Denzlinger, Michael Schäffer, Ulrich Wellhäußer, Ute Smith, Hans-Ulrich Markmann

Abstract


BACKGROUND: Prognosis of advanced hepatocellular carcinoma (HCC) is still poor. In this retrospective study prognostic factors for long-term survival and an immunohistochemical panel for discrimination of HCC from other liver malignancies were analyzed.

MATERIALS AND METHODS: In 181 primary liver tumors clinical data, tumor characteristics and the primary mode of treatment were analyzed using univariate and multivariate statistics. In 156 cases (145 HCC, 36 intrahepatic CCC) the immunohistochemical profile of the tumor tissue using molecular markers as HepPar-1, AFP, CD34, CK7, CK20, CA19-9 and CDX2 was established routinely. Significance of marker expression, sensitivity, specify and positive predictive value of the analyzed markers in relation to histological subtype were estimated using SPSS 10.0

RESULTS: Median overall survival (OS) was 15 ± 19.2 months. Multivariate analysis identified tumour size (p = 0.001), grading (p = 0.002), proliferative activity (Ki67 level; p = 0.032), multifocal tumour (p = 0.045), liver function (Child-Pugh score, p = 0.045) and performed tumour resection (p < 0.0001) as independent prognostic factors for survival. HepPar-1 was the most frequently expressed marker in HCC (positive in 71.8%; p < 0.0001) whereas positive AFP staining was less common (positive in 48.7%; p < 0.0001). The CD34 protein as a marker for vascular-associated tissue showed a positive reaction in 54.1% of tissues from HCC patients in comparison to 2 patients (6%) with cholangiocarcinoma (p < 0.0001).

CONCLUSIONS: Our data identified tumor stage, tumor biology and performed surgical therapy as independent prognostic factors for OS in HCC. Best predictive markers for differentiation between HCC and CCC were HepPar-1, CK7 and CA19-9. Using this panel fast and accurate differentiation by IHC was possible in more than 95% of the patients.


Keywords


Hepatocellular carcinoma; Ki67; proliferative activity; AFP; CK7; Immunohisto-chemistry (IHC)

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