Synchronous Hepatoblastoma, Neuroblastoma, and Cutaneous Capillary Hemangiomas: A Case Report.

Multiple synchronous tumors presenting in infancy raise concern for inherited or sporadic cancer predisposition syndromes, which include Beckwith-Wiedemann syndrome, familial adenomatous polyposis syndrome, and Li-Fraumeni syndrome. We report a case of a 7-month-old previously healthy male born following an in vitro fertilization-assisted twin pregnancy who presented with new-onset refractory shock, severe acidosis, and rapid decline over several hours. An autopsy revealed a ruptured liver involved by hepatoblastoma, an adrenal gland involved by neuroblastoma, and multiple cutaneous capillary hemangiomas. Standard genetic testing demonstrated that both twins were Gaucher disease (GD) carriers without evidence of other known cancer predisposition syndromes. This report describes a unique association of multiple synchronous tumors, which underscores the utility and importance of the pediatric autopsy. Moreover, given that the reported child was a GD carrier, the possibility the tumors were the result of a GD-mediated cancer-associated phenotype or an unrecognized sporadic clinical syndrome remains an unanswered, but intriguing, question worthy of further investigation.

Relationship of ß-catenin and postchemotherapy histopathologic changes with overall survival in patients with hepatoblastoma.

AIMS: Histopathologic spectrum and expression of ß-catenin were analyzed in patients with hepatoblastoma, diagnosed over a period of 14 years. These were correlated with the survival outcome. The morphologic features subsequent to chemotherapy were also analyzed. METHODS AND RESULTS: Histomorphologic features were studied on paraffin-embedded sections. There were 24 cases with 15 fetal, 4 embryonal, 4 macrotrabecular, and 1 of small cell subtype. Follow-up was available in 20 cases (mean = 16.8 mo). ß-catenin immunostaining performed by indirect immunoperoxidase method revealed 14 cases with nuclear and 10 cases with cytoplasmic positivity. Statistical analysis revealed no significant correlation between morphologic subtype and survival. Significant difference in survival was noted with respect to tumor stage, mitotic index, and ß-catenin staining pattern. Cases with nuclear expression had a mean survival of 71.54 ± 8.1 months in comparison with 14.71 ± 6.5 months in cases with cytoplasmic expression. Besides osteoid and cartilage formation, interesting postchemotherapy findings were the presence of tumoral maturation, hepatocellular carcinoma-like areas, peliotic-like foci, and "glomeruloid clusters." CONCLUSIONS: Nuclear ß-catenin expression is not a poor prognostic factor and this might be indicative of different genetic alterations in hepatoblastoma in the Indian subcontinent. There was no significant correlation between histologic subtype and osteoid differentiation with survival. The histopathologic changes observed were peliotic-like areas, tumoral maturation, hepatocellular carcinoma-like changes, and glomeruloid clusters besides the well-established features of osteoid differentiation after chemotherapy.

[Expression of GRP78 and GRP94 in the liver tissues and their clinicopathological significance in children with hepatoblastoma].

OBJECTIVE: To study the expression of glucose-regulated protin 78 (GRP78) and glucose-regulated protin 94 (GRP94) in the liver tissues from children with hepatoblastoma (HB) and to investigate the possible clinicopathological values of GRP78 and GRP94 in HB. METHODS: Liver tissue specimens from 15 children with HB and 10 specimens of normal liver tissues were obtained. EnVison immunohistochemistry was used to detect the expression of GRP78 and GRP94 in the conventional paraffin-embedded liver sections. RESULTS: The positive rates of GRP78 expression (53% vs 10%; P<0.05) and GRP94 expression (60% vs 10%; P<0.05) in HB liver tissues were significantly higher than those in the normal liver tissues. The positive rates of GRP78 expression in the cases without lymphnode metastasis or in clinical stage I-II were significantly lower than those in the cases with lymphnode metastasis or in clinical stage III-IV (P<0.05). GRP94 showed a decreased tendency of positive expression in the cases without lymphnode metastasis or in clinical stage I-II when compared with the cases with lymphnode metastasis or in clinical stage III-IV, although there were no statistical differences between them. CONCLUSIONS: GRP78 and GRP94 expression might play important roles in the pathogenesis and progression of pediatric HB.

Effects of neoadjuvant chemotherapy on hepatoblastoma: a morphologic and immunohistochemical study.

Neoadjuvant chemotherapy followed by resection has become the mainstay in the treatment of hepatoblastoma (HB). The changes after chemotherapy typically result in tumor necrosis and a fibrohistiocytic response. We have observed that treated HBs undergo additional morphologic changes that have not been described. Herein, we report a 15-year retrospective study of HBs in 22 children who received neoadjuvant chemotherapy according to the Children's Oncology Group protocols. The medical records, diagnostic imaging, and histopathology were reviewed. Besides treated HBs having characteristic necrosis and fibrohistiocytic response, two-thirds had areas of cytoarchitectural differentiation ("maturation") mimicking non-neoplastic liver, and a quarter had alterations mimicking hepatocellular carcinoma. Nuclear expression of beta-catenin and keratin profiles were useful in distinguishing residual tumor with "maturation" from non-neoplastic liver and therefore in the assessment of surgical margins. Statistical analysis revealed that larger pretreatment and posttreatment imaged tumor size, larger tumor size at pathologic examination, and vascular invasion were significant univariate predictors of metastatic disease, whereas pretreatment imaged tumor size and vascular invasion were also significant independent predictors (multivariate logistic regression analysis). Multifocality, greater posttreatment necrosis and hepatocellular carcinoma-like morphology were more often associated with metastatic disease, but did not reach statistical significance.

PAX immunoreactivity identifies alveolar rhabdomyosarcoma.

PAX5 is a member of the paired box transcription factors involved in development and its expression has been well characterized among hematopoietic malignancies of B-cell lineage. Its expression has also been reported in a subset of neuroendocrine carcinomas, urothelial tumors, Merkel cell carcinoma, glioblastoma, and neuroblastoma cell lines. As such, we sought to assess it as a diagnostic marker in the evaluation of pediatric small round blue cell tumors. Tumors selected for evaluation included embryonal rhabdomyosarcoma (55 cases), alveolar rhabdomyosarcoma (ARMS) (51 cases), neuroblastoma (22 cases), Wilms tumor (18 cases), Ewing Family of Tumors (11 cases), lymphoblastic lymphoma (8 cases), hepatoblastoma (6 cases), and granulocytic sarcoma (3 cases) as either cores in a tissue microarray or whole mount sections. All cases were immunostained using an antibody directed toward PAX5 and immunoreactivity was scored semiquantitatively according to percentage of nuclear staining. As expected, all B-cell lymphoblastic lymphomas were strongly immunoreactive against PAX5. Additionally, all Wilms tumors showed staining of variable intensity, most intensely in the epithelial component. Of the rhabdomyosarcoma cases, 34 of 51 (67%) ARMS were immunoreactive whereas none of the 55 embryonal rhabdomyosarcoma cases stained. No other tumor type on the array was immunoreactive toward PAX5. Genetic information was available on 7 ARMS, 5 of which had characteristic translocations involving PAX genes, either t(2:13) or t(1;13). Of the translocation-positive cases, all showed nuclear reactivity toward PAX5, and both the translocation-negative cases did not. Possible explanations of PAX5 staining include aberrant expression of the PAX5 transcription factor, PAX5 expression in normal tissue at the time the tumors most closely recapitulates in development or crossreactivity with another member of the PAX family. PAX3 and PAX7 fusion genes characterize the majority of ARMS making crossreactivity with these proteins an attractive theory, and suggest that PAX5 immunoreactivity may be specific for translocation-positive ARMS. Further study in a larger series of rhabdomyosarcomas is warranted to assess the sensitivity and specificity of PAX5 immunoreactivity for the ARMS variant.

Sporadic childhood hepatoblastomas show activation of beta-catenin, mismatch repair defects and p53 mutations.

Hepatoblastoma, a rare embryonic tumor that may arise sporadically or in the context of hereditary syndromes (familial adenomatous polyposis and Beckwith-Wiedemann's) is the most frequent liver cancer of childhood. Deregulation of the APC/beta-catenin pathway occurs in a consistent fraction of hepatoblastomas, with mutations in the APC and beta-catenin genes implicated in familial adenomatous polyposis-associated and sporadic hepatoblastomas, respectively. Alterations in other cancer-related molecular pathways have not been reported. We investigated a series of 21 sporadic paraffin-embedded hepatoblastoma cases for mutations in the p53 (exons 5-8) and beta-catenin (exon 3) genes, loss of heterozygosity at APC, microsatellite instability and immunohistochemical expression of beta-catenin and of the two main mismatch repair proteins, MLH1 and MSH2. No loss of heterozygosity at APC was detected. We found mutations in beta-catenin and p53 in 4/21 (19%) and 5/21 (24%) cases respectively, beta-catenin protein accumulation in 14/21 cases (67%), microsatellite instability in 17/21 cases (81%), of which eight resulted positive for high-level of microsatellite instability (in four cases associated with loss of MLH1/MSH2 immunostaining). No correlations between involved molecular pathway(s) and hepatoblastoma histotype(s) emerged. This study confirms that beta-catenin deregulation is involved in sporadic hepatoblastoma and also suggests that mismatch repair defects and p53 mutations contribute to this rare liver cancer. Sporadic hepatoblastoma appears to be molecularly and phenotypically heterogeneous and may reflect different pathways of liver carcinogenesis.

Inhibition of multiple gene expression and virus replication of HBV by stable RNA interference in 2.2.15 cells.

BACKGROUND/AIMS: Hepatitis B virus (HBV) infection is a world-wide health problem. Recent studies have demonstrated the efficacy of RNA interference (RNAi) against HBV replication at cell culture and animal levels using transient transfection. The present study was to determine whether the stable transfection of short hairpin RNA (shRNA)-producing vector could achieve potent and sustained inhibition of the HBV replication in 2.2.15 cells. METHODS: shRNA-producing vector against HBV and the empty vector were stably transfected into the 2.2.15 cells respectively. A series of experiments were performed in the producing stable lines to determine the changes of viral protein expression and replication. RESULTS: The HBV protein expression and viral replication were suppressed dramatically and stably by the integrated shRNA-producing vectors. Most importantly, this suppression effect persists after 30 passages. CONCLUSIONS: Our data provided the possibility of continuous and stable inhibition of HBV protein expression and replication in patients using RNAi, suggesting a potential clinical application of this novel approach. Furthermore, the established stable transfected cell lines provided a good platform for understanding the mechanism of anti-HBV by RNAi.

Raman spectroscopy for neoplastic tissue differentiation: a pilot study.

BACKGROUND: Several changes occur during the transformation of normal tissue to neoplastic tissue. Such changes in molecular composition can be detected by Raman spectroscopy. Raman spectroscopy is a nondestructive method of measuring these changes, which suggests the possibility of real-time diagnosis during medical procedures. METHODS: This study seeks to evaluate the ability of Raman spectra to distinguish tissues. The Raman signatures of normal kidney, lung, and liver tissue samples from pigs and rats were characterized in vitro. Further, a human neuroblastoma and a hepatoblastoma, obtained at resection were also studied. RESULTS: The Raman spectra of the animal samples of kidney, liver, and lung are distinctly different in the intensity distribution of the Raman peaks. Further, the spectra of a given organ from pigs and rats, although similar, were different enough to distinguish between the 2 animals. In the patient tissues, the Raman spectra of normal liver, viable tumor, and fibrotic hepatoblastoma were very different. Fibrotic tissue showed a greater concentration of carotenoids, whereas viable tissue was rich in proteins and nucleic acids. The normal tissue showed both components. Similar differences were also seen in the neuroblastoma tissue. CONCLUSIONS: The results of this study show the potential use of Raman spectroscopy in clinical diagnosis.

[Mechanism of arsenic trioxide-induced apoptosis in hepatic blastoma cells HepG2].

OBJECTIVE: To investigate the mechanism of arsenic trioxide (As(2)O(3)) induced apoptosis in hepatic blastoma cells HepG2 and its effects on cell nuclear matrix related protein promyelocytic leukaemia (PML). METHODS: HepG2 cells were cultured in MEM medium and treated with different concentrations of As(2)O(3) for either 24 h or 96 h. In situ terminal deoxynucleotidyl transferase (TdT) labeling (TUNEL) and DNA ladder were applied to detect apoptosis. Confocal microscopy and western blot were performed to observe the expression of PML. RESULTS: TUNEL positive apoptotic cells and DNA ladder could be detected in As(2)O(3) treated groups. The expression of PML decreased in HepG2 cells with 2 micro mol/L As(2)O(3), and micropunctates characteristic of PML protein in HepG2 cell nuclei almost disappeared after the treatment of 5 micro mol/L As(2)O(3). CONCLUSION: As(2)O(3) induces HepG2 tumor cell apoptosis in a time- and concentration-dependent manner. As(2)O(3) may degradate the PML protein in HepG2 cell nuclei. The decreased expression of PML is closely correlated with apoptosis. Nuclear matrix associated protein PML could be the target of As(2)O(3) therapy.

The oxidative biotransformation of losoxantrone (CI-941).

The oxidative biotransformation of the anticancer drug 7-hydroxy-2-[2-[(2-hydroxyethyl)amino]ethyl]-5-[[2-[(2-hydroxyethyl)amino]ethyl]amino]anthra[1,9-cd]pyrazol-6(2H)-one dihydrochloride (losoxantrone, CI-941) after incubation of primary cultures of rat hepatocytes has been investigated. The structures of twelve losoxantrone metabolites have been elucidated by means of high-performance liquid chromatography-mass spectometry, tandem mass spectrometry, and two-dimensional NMR. In these mammalian hepatocytes, the CI-941 biotransformation includes a monohydroxylation of the phenolic substructure of the CI-941-chromophore via cytochrome P450 catalysis, resulting in metabolites having an ortho- and para-hydroquinonoid substructure, respectively. The identification of a glutathione conjugate as a follow-up metabolite confirms the oxidative activation of the ortho-hydroxylated losoxantrone metabolite. The oxidative activation establishes the ability of CI-941 to form covalent bonds to intracellular nucleophilic targets. Furthermore, the CI-941 metabolism was shown to be extremely suppressed in rat hepatocytes incubated with metyrapone. In contrast to these results, human tumor HepG2 cells did not show any CI-941 biotransformation after incubation.

Albumin inhibits apolipoprotein AI and AII production in human hepatoblastoma cell line (Hep G2): additive effects of oleate-albumin complex.

Although the role of multiple humoral agents (such as plasma albumin, glucose, hormones etc.) are implicated in lipoprotein metabolism, the mechanism of action of these agents on various steps of the synthesis and secretion of lipoproteins and apolipoproteins (protein moieties of lipoproteins) are not completely understood. Specifically, the hepatocellular mechanisms of the effect of albumin and fatty acids on apolipoprotein (apo) AI and AII [major proteins of high density lipoproteins (HDL)] synthesis and secretion are not known. Using human hepatoblastoma cells (Hep G2) as an in vitro model system, this study examined the effect of albumin and fatty acids on the synthesis, secretion, and the steady-state mRNA expression of apo AI and AII. The data indicated that the incubation of Hep G2 cells with albumin, dose-dependently, inhibited apo AI and AII accumulation (secretion) in the media, de novo synthesis, and the steady-state mRNA expression. Albumin did not alter total protein synthesis; thus the effect of albumin appeared to be specific for the synthesis and secretion of apo AI and apo AII. Free fatty acids (FFA) are transported by albumin and diseases characterized by enhanced FFA mobilization (e.g. diabetes mellitus) are associated with low HDL levels. Studies were therefore performed to examine the effect of albumin-bound-oleic acid on apo AI and apo AII production. The results showed that the albumin-oleate complex further increased the inhibitory effects of albumin on apo AI and apo AII production. These data suggest how HDL metabolism may be affected at the hepatocellular level by alterations in plasma albumin concentrations and/or fatty acid mobilization in clinical situations characterized by altered HDL levels.

In vivo expression of soluble Fas and FAP-1: possible mechanisms of Fas resistance in human hepatoblastomas.

Many tumour cells express both Fas and its ligand (FasL) on their surface and it has remained a mystery why such cells do not simply kill themselves. It remains to be determined whether Fas and FasL are expressed in human hepatoblastomas and if so, what is responsible for the possible Fas resistance of these tumours. In this study, the expression of Fas and FasL was examined in 23 cases of human hepatoblastoma by immunohistochemical staining. To elucidate possible Fas resistance in hepatoblastomas, Fas-resistance pathways including the expression of bcl-2 and Fas-associated phosphatase-1 (FAP-1), and the expression of soluble Fas (sFas) mRNA, were analysed by immunohistochemistry and in situ reverse transcription-polymerase chain reaction (in situ RT-PCR). Fas gene mutation in the death domain was also examined. Fas and FasL were expressed in all hepatoblastomas analysed. Twenty (87 per cent) and 18 (78 per cent) cases of hepatoblastoma were positive for sFas mRNA and FAP-1, respectively, but none of the hepatoblastomas expressed bcl-2. Mutation in the death domain of the Fas gene was not found in hepatoblastomas. Taken together, these findings demonstrated that Fas, a death receptor, and its ligand are co-expressed in hepatoblastomas in vivo, but some inhibitors of Fas-mediated apoptosis are also expressed in these tumours. These results suggest that it is probably due to the action of inhibitory molecules of the Fas pathway that the tumour cells of hepatoblastomas do not kill themselves in an autocrine-driven cycle and that in this manner hepatoblastomas avoid apoptosis.

Paclitaxel: an effective antineoplastic agent in the treatment of xenotransplanted hepatoblastoma.

BACKGROUND: Hepatoblastoma is an uncommon liver tumor of infancy and early childhood. Though most patients with nonmetastatic hepatoblastomas can be cured by defining surgical strategies and chemotherapy regimes, new drugs are needed for children with advanced hepatoblastomas. The activity of paclitaxel as a new antineoplastic agent with limited experience in pediatric oncology was studied in a xenograft model. PROCEDURE: Hepatoblastoma cell suspensions from three children were transplanted subcutaneously into nude mice NMRI (nu/nu). One of the primary tumors was an embryonal multifocal hepatoblastoma, whereas the other tumors were embryonal/fetal hepatoblastomas localized on a liver lobe. After 4 weeks, xenografted tumor sizes reached 50-100 mm3. The xenografted tumors resembled their originals histologically and produced high levels of alpha-fetoprotein. The efficiency of paclitaxel at equitoxic doses was analyzed. RESULTS: Paclitaxel produced an effect in all three hepatoblastomas. There was a significant reduction of tumor volume (P < 0.001) and alpha-fetoprotein levels after chemotherapy (P < 0.0001). The proliferation activity of the tumor cells corresponded with these results. Histologically, after treatment with paclitaxel the tumor regression was 35%-49%. The mechanism of paclitaxel action could be demonstrated by light microscopy immunohistochemistry and electron microscopy. CONCLUSIONS: The preliminary results in phase I trials of solid tumors in children and the results of this study suggest that paclitaxel in phase II studies can now be entertained for patients with hepatoblastoma.

Comparative activity of cisplatin, ifosfamide, doxorubicin, carboplatin, and etoposide in heterotransplanted hepatoblastoma.

BACKGROUND: Hepatoblastoma is the most common primary malignant liver tumor affecting infants and young children. Recent clinical experience with advanced hepatoblastoma shows that a reliable in vivo model to study the tumor's response to drugs is needed urgently. METHODS: Hepatoblastoma cell suspensions from three children were transplanted subcutaneously into NMRI nude mice (nu/nu). One of the primary tumors was a embryonal multifocal hepatoblastoma, whereas the other tumors were embryonal/fetal hepatoblastomas localized to one liver lobe. The xenograft tumors resembled their original tumors histologically and produced high levels of alpha-fetoprotein. The mice who received the tumors were given ifosfamide, cisplatin, doxorubicin, carboplatin, and etoposide as single agents. Thereafter, the tumor growth rate and alpha-fetoprotein levels in the animal sera were measured before and after chemotherapy and compared with the control group. After chemotherapy, the tumors were studied by conventional histology. RESULTS: The tumors in the nude mice derived from the multifocal hepatoblastoma reacted minimally against four of the five cytotoxic agents, whereas cisplatin reduced the tumor volume significantly. There was a marked reduction in tumor volume in the other tumors after application of cisplatin and doxorubicin, respectively. The tumors displayed a moderate reduction in size after treatment with ifosfamide, etoposide, and carboplatin. The responses to the different cytostatic agents also corresponded with serum alpha-fetoprotein levels and mitotic rates in the tumor cells. CONCLUSIONS: To the authors' knowledge, this is the first time an in vivo model for analyzing the effects of chemotherapy on hepatoblastoma has been established. The animal model may be suited for the evaluation of new drugs for the treatment of hepatoblastoma and for the investigation of multidrug resistance mechanisms in hepatoblastoma.

Placental involvement in congenital hepatoblastoma.

We describe extensive placental involvement by hepatoblastoma in a 2600 g, 33-week estimated gestational age (EGA) hydropic female fetus with the hepatoblastoma otherwise limited to the liver. The placenta weighed 1190 g and histopathologic examination revealed diffuse tumor emboli in chorionic villous vessels. The placental tumor exhibited a cytologic appearance similar to the primary tumor and showed strong alpha-fetoprotein staining. Although unusual, other congenital tumors, including neuroblastoma and leukemia, have also been described metastatic to the placenta. This case emphasizes the important role of careful histopathologic examination of the placenta which, combined with immunohistochemistry and clinicopathologic correlation, may establish a diagnosis and possibly obviate the need for invasive neonatal diagnostic procedures.

Immunohistochemical evaluation of hepatoblastomas with use of the hepatocyte-specific marker, hepatocyte paraffin 1, and the polyclonal anti-carcinoembryonic antigen.

The distinction of hepatoblastoma, especially the embryonal type, from other small, round-cell tumors of childhood can sometimes be difficult. Polyclonal anticarcinoembryonic antigen (pCEA) and Hepatocyte Paraffin 1 (Hep Par 1) are immunohistochemical markers that are useful in the diagnosis of hepatocellular carcinomas. We immunohistochemically studied pCEA, monoclonal CEA (mCEA), and Hep Par 1 on 12 hepatoblastomas (3 fetal type, 2 embryonal type, and 7 mixed epithelial type). In addition, we studied the expression of Hep Par 1 on 27 other selected childhood tumors, including 1 hepatocellular carcinoma, 5 germ-cell tumors, 4 peripheral neuroectodermal tumors/Ewing's sarcomas, 3 rhabdomyosarcomas, 5 neuroblastomas, 2 rhabdoid tumors, 3 lymphomas, and 4 Wilms' tumors. All of the hepatoblastomas expressed Hep Par 1 with a characteristic granular intracytoplasmic pattern that was generally less intense in embryonal-type than in fetal-type hepatoblastomas, perhaps reflecting the degree of hepatocyte differentiation. All of the fetal-type hepatoblastomas expressed pCEA with both an intracytoplasmic and bile canalicular pattern. Embryonal type hepatoblastomas were more likely to be pCEA negative or to show focal or no canalicular pattern of expression, again possibly reflecting the degree of hepatocyte differentiation. All of the hepatoblastomas were mCEA negative. All of the nonhepatoblastomas were Hep Par 1 negative, except for the one hepatocellular carcinoma in this study, which was Hep Par 1 positive. We conclude that Hep Par 1 and pCEA are useful markers for hepatoblastomas, as they have been shown to be in hepatocellular carcinomas.

Cytogenetic abnormalities and clonal evolution in an adult hepatoblastoma.

Hepatoblastomas usually occur in children < 3 years of age, and only occasional adult cases have been described. To date, 20 cytogenetically abnormal childhood hepatoblastomas have been reported. Karyotypic investigations have shown that most hepatoblastomas are diploid or hyperdiploid, often displaying trisomies for chromosomes 2 and 20. We have cytogenetically investigated an adult hepatoblastoma for which no previous karyotypic data exist. A hypertriploid stemline with multiple numerical and structural chromosomal aberrations, including +2 and +20, was found. In addition, the tumor displayed extensive clonal evolution with 11 subclones. Although the tumor thus displayed some chromosomal abnormalities commonly observed in childhood tumors, providing further support for the importance of these abnormalities in the development of hepatoblastoma, the level of genomic complexity seen in the present case has never been described in childhood hepatoblastomas and may suggest a different etiology or pathogenesis.

Hepatoblastoma in a dog.

A hepatoblastoma was found in a 13-year-old female Maltese dog. Histologically, the tumor showed a wide trabecular pattern and was frequently accompanied with vascular lake formation. Tumor cells were positive for cytokeratin and neuron specific enolase, but negative for chromogranin. Electronmicroscopically, tumor cells were accompanied with continuous basement membrane and had poorly developed desmosomes. Sinusoidal endothelia had fenestration and were surrounded by myofibroblast-like cells. To the best of our knowledge, this paper is the first report of morphological studies on canine hepatoblastoma.

Expression of cell adhesion molecules and common acute lymphoblastic leukaemia antigen in hepatoblastoma.

Hepatoblastoma is an embryonal tumour of the liver, which often contains tissue components with multidirectional differentiation. The occurrence of cell surface antigens in this tumour has not been studied systematically, and we therefore investigated 20 hepatoblastomas for the expression of common acute lymphoblastic leukaemia antigen (CALLA) and cell adhesion molecules (CAMs) in their different tissue components. Epithelial tumour cells of fetal differentiation contained E-cadherin. This protein did not occur in tumour areas with embryonal or mesenchymal differentiation. In contrast, immature embryonal and anaplastic cells expressed CALLA and the hyaluronate receptor (HCAM, CD44). Both fetal and embryonal areas stained irregularly positive for ICAM-1, which, in contrast, was not present on anaplastic cells. Immature fibrous tissue did not contain any of these molecules except for ICAM-1. However, some cells adjacent to, or enclosed in, osteoid were positive for HCAM and NCAM. Like small undifferentiated hepatoblastoma cells, primitive mesenchymal spindle-shaped cells also expressed CALLA, HCAM, and the polysialylated embryonic form of NCAM strongly. This last is not present on other epithelial or mesenchymal tumour cells. Hepatoblastoma cells of varying differentiation express distinct patterns of CAMs and CALLA. Our results give further insight into their histogenesis and cellular interactions and may explain their variable ability for invasive growth and formation of metastases.