Elsevier

Hepatology Research

Volume 20, Issue 3, July 2001, Pages 312-319
Hepatology Research

Immunoreactivity to monoclonal antibody, Hep Par 1, in human hepatocellular carcinomas according to histopathological grade and histological pattern

https://doi.org/10.1016/S1386-6346(00)00147-9Get rights and content

Abstract

We evaluated the immunoreactivity to monoclonal antibody for hepatocyte (Hep Par 1) and determined the cellular distribution of the antigen in hepatocellular carcinoma (HCC), based on the histopathological grade and histological pattern. The pathological material included 100 areas selected at random in 61 tissue sections from 12 autopsy livers with HCC. Immunoreactivity was classified into four categories; strongly positive (>90% of the area showed positive staining), moderately positive (5–90% of the area), weakly positive (<5% of the area), and negative (completely negative). All 19 (100%) well-differentiated, trabecular type HCC areas were strongly positive for Hep Par 1. Among 11 well-differentiated, pseudoglandular type HCC areas, 2 (18%) were strongly positive, 5 (46%) were moderately positive, 2 (18%) were weakly positive, and 2 (18%) were negative. Among 36 moderately differentiated, trabecular type HCC areas, 6 (17%) were strongly positive, 17 (47%) were moderately positive, 9 (25%) were weakly positive, and 4 (11%) were negative. None of the four moderately differentiated, pseudoglandular type HCC areas were strongly positive, 3 (75%) were moderately positive, 0 was weakly positive, and 1 (25%) was negative. Among 25 poorly differentiated, compact or trabecular type HCC areas, 15 (60%) were weakly positive and 10 (40%) were negative. All 5 (100%) undifferentiated HCC areas were negative for Hep Par 1. Our results indicate that immunoreactivity to Hep Par 1 in HCC decreases with reduced differentiation of the tumor, suggesting that Hep Par 1 monoclonal antibody is useful as a marker for the diagnosis and differentiation of HCCs.

Introduction

In 1993, Wennerberg et al. [1] prepared a new monoclonal antibody, hepatocyte paraffin 1 (Hep Par 1), which reacted with both normal and neoplastic hepatocytes in formalin-fixed, paraffin-embedded tissue sections. The use of this antibody resulted in a distinct, granular cytoplasmic staining of hepatocytes but did not stain bile ducts or non-parenchymal liver cells. Since then, the antibody has been used to differentiate primary liver tumors from metastatic liver tumors, as well as hepatocellular carcinoma (HCC) from cholangiocarcinoma or combined tumors [2], [3]. It has been also used to study liver development [4] and liver regeneration [5]. Therefore, Hep Par 1 is a useful antibody for pathological diagnosis and investigation of liver tumors.

To our knowledge, all studies that have so far used Hep Par 1 for HCCs reported that the antibody reacts with almost all HCCs, irrespective of the degree of differentiation [3], [6]. Detailed analysis of the staining pattern of HCC based on histopathological grade has not yet been reported. In the present study, we analyzed Hep Par 1 immunoreactivity in HCCs based on histopathological grade and histological pattern.

Section snippets

Materials and methods

Liver tissues were obtained from 12 autopsy cases of primary HCC. The patients’ age at death ranged from 48 to 82 years (average, 63.8 years), and male:female ratio of 11:1. In 11 cases, HCC was associated with liver cirrhosis. A total of 61 tissue blocks were obtained from HCC areas in these cases. The liver specimens were fixed in 10% neutral buffered formalin solution and embedded in paraffin. They were then cut into 4-μm-thick sections and mounted on 3-aminopropyltriethoxysilane coated

Histological grade and pattern

Using the histopathological grade and histological pattern defined above, we classified H–E/Gomori stained sections of HCC into six different categories, (1) well-differentiated HCC of trabecular type (W and T); (2) well-differentiated, pseudoglandular type (W and P); (3) moderately, trabecular type (M and T); (4) moderately, pseudoglandular type (M and P); (5) poorly, compact or trabecular type (P and C); and (6) undifferentiated carcinoma type (U). The number of areas in each category is

Discussion

Wennerberg et al. [1] reported that Hep Par 1 reacted with almost all HCCs with the exception of one case of sclerosing HCC. However, they did not describe the reactivity based on histopathological grade or structural pattern. In the present study, we found that (1) well-differentiated, trabecular type HCCs were always strongly positive for Hep Par 1 and showed a similar reactivity to non-tumorous trabecular hepatic cord; (2) immunoreactivity to Hep Par 1 in HCC diminished with decreased

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