Coexistence of HFE and rare UGT1A1 genes mutations in patients with iron overload related liver injury.

This report describes two patients hospitalised in Hepatology Unit, Infectious Diseases Department Medical University of Gdansk because of liver damage discovered in family doctor's practice. Hereditary hemochromatosis was diagnosed in both cases. Diagnosis was established basing on medical records review, and biochemical, molecular and liver specimen tests. The analysis of polymorphism of UGT1A1 gene was done in these cases because those patients were a part of the larger study on prevalence of UGT1A1 gene mutations in patients with hereditary hemochromatosis. We discovered rare variant forms of UGT1A1 gene coexisting with HFE gene mutations.

The role of immunohistochemistry in histopathological diagnostics of clinically "silent" incidentally detected adrenal masses.

BACKGROUND: The detectability of adrenal incidentalomas (incidentally found adrenal tumours) in the whole population is estimated at 0.1%; 0.42% in non-endocrine patients and at 4.3% in oncologically diagnosed ones. Even up to 16% of incidentalomas of adrenal glands can be malignant lesions. The issue of crucial importance is the histopathological differentiation between benign lesions and malignant tumours of the adrenal cortex and medulla. OBJECTIVES: To evaluate whether the immunohistochemical analysis of the expression of p53, p21, PCNA and Ki67 in the tumour's tissue can be useful in the histopathological diagnostics of adrenal incidentalomas and whether it is important for prognosis. MATERIAL AND METHODS: Our series consisted of 74 tumour samples from 164 patients operated for incidentalomas. There were 43 cortical adenomas, 11 cortical adrenocarcinomas and 20 PHEOs (including 5 malignant lesions). Using monoclonal antibodies, the expression of p53, p21, PCNA and Ki67 was evaluated. RESULTS: We found a statistically significant correlation between the expression of p53, p21, Ki67 and the differential diagnosis of adrenal cortical adenoma and adrenocortical carcinoma (for proteins: p53 p=0.010, for p21 p=0.010, for Ki67 p<0.001). The statistical significant correlation between PCNA protein and diagnosis of adrenal cortical adenoma and adrenocortical carcinoma was not found. The statistically significant correlation between p21, PCNA proteins and the diagnosis of benign and malignant PHEOs was not estimated. There was no expression of Ki67 or p53 protein above the assumed level in benign and malignant pheochromocytomas. The statistically significant correlation between p53, p21, PCNA or Ki67 and the occurrence of metastases in adrenocarcinoma and malignant PHEOs was not found.

Primary malignant fibrous histiocytoma of the lung.

BACKGROUND: Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma in adults. Its appearance as a primary lung tumor is extremely rare. The cell origin of MFH remains controversial. The treatment of choice for MFH is surgical resection, while the role of chemo- and radiotherapy remains unclear. METHODS: A retrospective analysis of 5 patients operated on for primary MFH in the Department of Thoracic Surgery of the Medical University in Gdansk between 1990 and 2000 was performed. RESULTS: Out of approximately 2000 patients operated on for primary malignant lung tumors, five (0.25 %) had MFH. The mean age of the 4 men and 1 woman was 62 years. In all cases radical resection was performed without adjuvant chemo- or radiotherapy. Four patients died within 2 - 7 months after the operation, three of them from distant metastases. The follow-up of one patient is not available. One patient is alive 11 years after the operation. CONCLUSION: Although surgical resection of MFH is the treatment of choice in MFH, the results are unsatisfactory.

Application of sulforaphane: histopathological study of intraportal transplanted pancreatic islets into livers of diabetic rats.

BACKGROUND: Islet cell transplantation is a promising method to restore insulin independence to patients with type 1 diabetes mellitus. A main problem in clinical islet transplantation is the fact that only a small percentage of allogeneic islet-transplanted type 1 diabetic patients can completely omit insulin injections after transplantation. One reason for the impaired survival of islet grafts is aberration of the function of islets due to toxic agents, including oxygen radicals and nitric oxide, which arise during warm or cold ischemic time. Therefore, in clinical islet transplantation, islets have been preserved with a mixture of antioxidants to reduce free radical-mediated damage of transplanted beta cells. Our aim was to examine hepatic tissue after metabolic normalization following intraportal islet transplantation after application of sulforaphane. MATERIALS AND METHODS: Islets were isolated from pancreata of WAG rats. Sulforaphane (24 mg/kg) was administered 24 hours before isolated islets were transplanted into the liver through the portal vein (1200 +/- 100 per rat). At 9 months after transplantation the animals were killed and liver tissue removed for morphological examination. RESULTS: This report indicated that the intrahepatic portal vein site was indeed an excellent locus for implantation of free pancreatic islets. The islet grafts developed rich vascularization derived from both venous and arterial sources. The islet cells maintained their structural and functional integrity after implantation. CONCLUSION: Our results showed that sulforaphane improved islet function in vivo, indicating that combination of a free radical scavenger and an antioxidant (sulforaphane) may be used to increase the effectiveness of islet transplantation.

Nonalcoholic fatty liver disease treated by gastroplasty.

Nonalcoholic steatohepatitis (NASH), which is the most severe histologic form of nonalcoholic fatty liver disease (NAFLD), is emerging as the most common clinically important form of liver disease in obese patients. The prevalence of NASH may increase with the rise in the rate of obesity and metabolic syndrome in affluent communities. The aim of this work is to describe clinical and histopathologic findings and correlate liver tissue damage to the length of duration of the obesity in the group of patients who underwent surgery as obesity treatment. Eighty-seven severely or morbidly obese patients underwent gastroplasty. Each patient was evaluated with complete clinical and laboratory medical assessment together with wedge liver biopsy taken from 59 unselected patients during the surgery. Patients were followed up for 41 months. Repeat liver biopsy was taken from 10 patients. Pathologic analysis recorded the presence and degree of steatosis, portal and lobular inflammation and fibrosis. Age, body mass index (BMI), and laboratory assessment correlated with pathologic data. Male patients showed more pronounced metabolic syndrome and fatty liver damage. Patients who become obese in childhood or as teenagers showed no differences in metabolic syndrome and NAFLD in mature age. There was statistically significant association between BMA, elevated transaminases, NAFLD, and fibrosis. Significant weight reduction was observed within first year after surgery, was slower in the second year, and stabilized within third year. Remarkable improvement followed in biological markers of metabolic syndrome. Ninety-six percent of initial liver biopsies had steatosis; 16% developed steatohepatitis and mild perivenular fibrosis. Significant improvement of the degenerative and inflammatory hepatic lesions in repeated biopsies and liver function readings was noted within 8 months after surgery. Obesity is a major and independent risk factor for the metabolic syndrome, NAFLD, NASH, and fibrosis. Surgical treatment improves metabolic abnormalities and hepatic lesions in long-term observations.

Clinical significance of apoptotic index in non-small cell lung cancer: correlation with p53, mdm2, pRb and p21WAF1/CIP1 protein expression.

PURPOSE: The aim of this study was to assess the prognostic relevance of apoptotic index (AI), considered alone or together with expression of several proteins controlling G1 check point (p53, mdm2, pRb and p21WAF1/CIP1) in non-small cell lung cancer (NSCLC) patients. METHODS: Study group included 50 NSCLC patients who underwent curative pulmonary resection. Apoptosis was detected with the use of TUNEL technique and AI was defined as the number of apoptotic cells per 1,000 tumor cells. The expression of p53, mdm2, pRb and p21WAF1/CIP1 was assessed immunohistochemically. RESULTS: The mean and median AI calculated for all 50 patients was 14 and 9, respectively. Patients with lower (<14) and higher (> or =14) AI constituted 35 (70%) and 15 (30%) of cases, respectively. AI was not correlated with patient clinical characteristics, and expression of p53, pRb and p21WAF1/CIP1 . However, lower AI was correlated with over-expression of mdm2 protein (P=0.04). Median survival for patients with lower and higher AI was 43 months and 22 months, respectively, and 5-year survival probability-60 and 25%, respectively (P=0.03). In multivariate analysis, the only variable associated with shortened survival was AI (P=0.03, HR=2.9, 95% CI 1.95-3.86). CONCLUSIONS: These results suggest that AI correlates with mdm2 protein expression and influences survival in NSCLC.

Nesidioblastosis--a rare cause of hypoglycaemia in adults.

A case of suspected clinically hormonally active insulinoma in a 48-year-old woman is presented. Despite the lack of features, which might correspond to the insulinoma in radiological examinations, the patient was qualified for a distal subtotal pancreatectomy and then, due to persistent hyperinsulinism, for total pancreatectomy. The insulinoma was found neither in a palpable examination of the pancreas nor in the intraoperative ultrasonic examination. In a histopathological examination supplemented with immunohistochemical tests, nesidioblastosis - a rare cause of hypoglycaemia in adults - was diagnosed.

Overexpression of cathepsin B correlates with angiogenesis in colon adenocarcinoma.

Some studies have shown the influence of proteases and vascular density in colorectal primary tumors on spreading and on the course of colorectal cancer. In the present study we have analyzed the relationships between overexpression of cathepsin B protein and angiogenesis intensity in resected colon tumors and their impact on prognosis. It has been investigated in a series of 90 colon cancer patients. Immunohistochemistry was used to evaluate cathepsin B overexpression in cancer cells and to visualize microvessels with antibodies against von Willebrand factor. Overexpression of cathepsin B was observed if more than 50% of cancer cells in searched field showed immunoreactivity with antibody against cathepsin B. Intensity of angiogenesis was evaluated as a mean number of microvessels from three fields with highest vessel number. In 36 cases (40%) overexpression of cathepsin B was detected. Increased angiogenesis (above median 31 vessels per 0.785 mm2) correlated positively with cathepsin B overexpression (p=0.0006). Higher vascular density associated with the presence of metastases in regional lymph nodes (p=0.01). Overexpression of cathepsin B was observed more often in group of older people (age above median 65 years; p=0.005). According to univariate analysis metastases in regional lymph nodes (p=0.0007), increased angiogenesis (p=0.0085), and distant metastases (p=0.02) were the features potentially influencing prognosis. Multivariate analysis revealed independent prognostic value only in case of metastases in regional lymph nodes (p=0.013) and when distant metastases were present (p=0.021), but not when increased angiogenesis in primary colon adenocarcinoma was observed (p=0.078). In conclusion we can say that there is a close relationship between intensity of angiogenesis and overexpression of cathepsin B protein in cancer cells in resected colon adenocarcinoma.

[Focal nodular hyperplasia of the liver in a young female]. / Ogniskowa hiperplazja watroby u mlodej kobiety.

Focal nodular hyperplasia (FNH) of the liver is a lesion characterized by a well circumscribed region of hyperplastic liver tissue with stellate fibrosis. The pathogenesis of FNH is unknown but various authors consider that this lesion may be a response to a preexisting vascular abnormality. A 27-year-old woman was referred because of large liver lesion detected by ultrasound abdominal examination. Doppler ultrasound, computed tomography and magnetic resonance suggested this was FNH. The patient was conducted to resection of the tumor because of size of the tumor and presence of clinical signs and symptoms. Pathological examination of the surgical resection confirmed diagnosis of FNH. Follow-up after 1 and 2 years showed that the patient remained well but she complained of general weakness and we found unexplained elevation of GGT. Liver biopsy was performed 1 year after resection of the tumor and histopathological examination showed only minimal reactive changes.

[Meningiomas of the nose and paranasal sinuses]. / Oponiaki nosa i zatok przynosowych.

In material of ENT Department, Medical University of Gdansk we have three cases of extracranial meningioma localized in the nose and sinuses. Two of them are presented in this paper. One case was 29 year woman with meningioma of the nose and ethmoid and maxillary sinuses; it was residual tumor after removal of intracranial meningioma 3 years earlier. Second case was 14 year boy with meningioma of the nose, ethmoid and maxillary sinuses and of the orbit. In both patients tumor was removed by rhinosurgical access (lateral rhinotomy). Late results of the operation were very good. Basing on clinical and radiological pictures of both cases, pathological characteristics of naso-sinusal meningioma was made.

Lymphoid aggregates in gastric biopsies: relationship to other mucosal lesions.

The purpose of this study is to estimate the prevalence of lymphocyte aggregates (precursor of MALT lymphomas) in gastric mucosal biopsies and to associate gastric lymphoid tissue with the age of patients, Helicobacter-associated gastritis and other gastric mucosal pathology. A consecutive series of gastric mucosal samples from 150 children and 256 adults were assessed for the presence of lymphoid aggregates as well as morphological characteristics, Helicobacter pylori status, signs of gastritis, mucosal atrophy and lymphoepithelial lesions. Fifteen selected samples with prominent lymphoid aggregates and 10 controls were examined immunohistochemically for the immunoglobulins A, G, M, lymphocytes B and T, clonality of B cell population, atypical lymphocytes and Epstein-Barr virus (EBV) antigen. There was an increase of H. pylori infection and mucosal lymphoid aggregates (MALT) rates in parallel with the increasing age of patients noted in the histological assessment of the mucosal samples. A close association of lymphoid aggregates with H. pylori infection and prominent active gastritis was found, but in adults with chronic non-active, particularly atrophic gastritis this association became weaker. No morphological and immunohistochemical signs of MALT lymphoma were present. Lymphoid aggregates in children were larger, with follicles, but less numerous and tended to be located in the intermediate and deeper parts of the gastric mucosa. Immunohistochemical studies showed an increase of IgA, IgM and lymphocytes T in the deeper part of the lamina propria in H. pylori-associated gastritis and lymphocyte T accumulation in the periphery of the lymphoid follicles. No evidence of monoclonality, CD31 positive lymphocytes or EBV antigen was detected. Lymphoid aggregates are related, but not exclusively, to H. pylori infection. Their detection rates achieve a peak in young adults with H. pylori infection. Lymphocytic aggregates are also present in chronic atrophic gastritis without H. pylori infection and may relate to autoimmune inflammatory response to other factors.

Proliferative activity of normal and neoplastic colonic mucosa in population groups with high and low risk for colorectal carcinoma.

Europeans have a high incidence of colorectal cancer in comparison to Africans. Lack of detectable sequence adenoma-colorectal carcinoma in Africans may suggest the development of adenocarcinoma is de novo. The aim of this study is to assess colonic mucosal proliferative activity in various pathological conditions of diverse population groups. Materials included routinely processed tissue specimens from consecutively resected well- and moderately differentiated colorectal adenocarcinomas from 32 rural Africans (South Africa) and 27 urban Europeans (Poland) and from apparently normal rectal mucous membrane from the age and sex matched each population group (28 and 25 samples respectively). In addition, 32 resected adenomatous polyps were examined in Europeans as well. The MIB 1 monoclonal antibody was used to assay the expression of Ki67 antigen in routinely processed tissue specimens. Proliferative activity in colonic carcinomas was scored by the percentage of positively stained cells. Labelling indices were estimated in 5 crypt compartments in apparently normal colonic mucosa adjacent and distant to the tumour, in mucosal samples of controls from both population groups and in adenomatous polyps from Europeans. The mean age of African patients with adenocarcinoma was markedly lower than in European counterparts (48.6 yrs vs. 66.4 yrs). The overall proliferative activity in cancerous tumours of Africans was higher than in Europeans. The labelling indices were lower in all compartments in normal colonic mucosa in Africans. Overall increase of the labelling indices in adjacent and distant to the tumour mucosa noted when compared to the mucosa of healthy individuals. No such differences were detected between indices in the mucosa adjacent and the mucosa distant to the tumour. Proliferative activity in the mucosa adjacent to adenoma was also higher than in normal mucosa from healthy individuals. Adenomas with marked dysplasia showed higher and diffuse proliferative activity, when regular adenomas shown superficial labelling only. Relatively young age, lack of detectable evidence of adenoma-carcinoma sequence and low proliferative activity in all compartments of mucosa from healthy individuals indicate different etiopathogenesis of colorectal carcinoma in rural Africans.

Changes in acid secretion over the years. A 30-year longitudinal study.

We studied the effect of aging on gastric acid secretion in 11 physicians who had augmented histamine tests while at medical school in 1962. One of them had a duodenal ulcer at the time. The augmented histamine test was repeated in 1991 and, in addition, upper gastrointestinal endoscopy was done to exclude peptic ulcer and to obtain biopsies for histologic analysis and assessment of Helicobacter pylori status. The mean basal acid output decreased from 7.3 to 1.9 mEq/hr during the 30-year period of follow-up (p < 0.001), and the mean maximum acid output decreased from 29.9 to 20.3 mEq/hr (p < 0.01). The maximum acid output data showed a profound decrease in 4 of the 11 participants, a lesser decrease in 4, and a minimal increase in the remaining 3. Histologic analysis suggested a greater likelihood of atrophic gastritis, H. pylori infection, or both in participants showing a pronounced decrease in acid secretion with aging.

Hepatic siderosis, fibrosis and cirrhosis: the association with hepatocellular carcinoma in high-risk population.

Iron overload has been shown to impair the immune response of the liver, and induce hepatic fibrosis and cirrhosis. Opinions differ concerning the relative risk of developing hepatocellular carcinoma (HCC) in siderotic patients as compared with patients with hepatic fibrosis and cirrhosis and the possible mechanism of liver carcinogenesis in genetic hemochromatosis is still unknown. The purpose of this study is to assess hepatic iron overload, fibrosis and cirrhosis in liver tissue adjacent to hepatocellular carcinoma and in liver tissue of controls in population at risk for hepatocellular carcinoma. Liver tissue was available for examination in 147 biopsies with HCC collected in South Africa. As controls we used liver samples from 211 age and sex matched Africans who died in accidents. Tissue samples were processed routinely, stained with H and E, Sweet's reticulin, Masson's trichrome for fibrous tissue, Prussian blue for iron stain and immunohistochemically for HBsAg. Iron content was assessed with the method described by Brissot. Iron overload was detected in 42.1% of cancerous livers and in 43.7% of livers from controls. The presence of siderosis and iron content gradually increased with the age of studied similarly in cases and in controls. Cirrhosis was present in 32% of cancerous livers and was associated with iron overload in 13%. No cirrhosis and 6% of mild periportal fibrosis not related with siderosis was observed in controls. HBsAg was stainable in 80% of cancerous livers of patients below 25 years of age and in 40% of patients over 35 years. HBsAg in controls was positive in 9%. No relationship of HBsAg and amount of stainable iron in cancerous and livers of controls was found. In conclusion, African siderosis can not play important role in the etiopathogenesis of HCC.

Increased matrix proteins, collagen and transforming growth factor are early markers of hepatotoxicity in patients on long-term methotrexate therapy.

BACKGROUND: Hepatotoxicity, which may lead to fibrosis and cirrhosis, often limits the use of long-term low dose methotrexate for psoriasis and autoimmune diseases. Standard light microscopy lacks sensitivity for early fibrosis. DESIGN: This is a retrospective study of immunohistochemical markers of early fibrosis including laminin and fibronectin, collagen deposition and lipocyte activation in hepatic biopsies of 36 psoriatic patients treated with methotrexate for one to five years, at an average dose of 20 mg/week. Biopsies before initiation of methotrexate (n = 36) showed minimal immunohistochemical expression of desmin, transforming growth factor alpha, matrix proteins, and collagen. Expression of laminin, fibronectin, collagens III and IV increased significantly and progressively over baseline values after cumulative doses of 1.5 +/- 0.25 g (n = 20) and 3 +/- 0.5 g methotrexate, respectively. Increases in desmin, smooth muscle actin and collagen type I also occurred but the changes were less consistent. Light microscopic abnormalities of hepatotoxicity were not detectable in any of these biopsies. CONCLUSIONS: Immunohistochemical quantification of matrix proteins and collagens type III and IV may be early, sensitive and dose responsive markers of methotrexate hepatotoxicity which progress with increasing cumulative doses of methotrexate.

Histological findings in gastroduodenal mucosa in patients with Crohn's disease. Any diagnostic significance?

Histological observation of the gastroduodenal mucosa in 54 patients with Crohn's disease is reported. The medical or surgical history was available in all patients. Biopsy specimens collected during gastroduodenal endoscopy were fixed in 10% buffered formalin, processed routinely and stained with HE, paS/AB, and modified Giemsa stain and assessed microscopically. Patchy/focal active gastritis or duodenitis was the most consistent microscopic finding. About 1/4 of patients with gastric biopsies presented crypt atrophy, lymphoid tissue proliferation, fibrosis of the lamina propria, foveolar hyperplasia, intestinal metaplasia, erosions or ulcerations. Erosions/ulcers, villous atrophy, fibrosis, lymphoid tissue proliferation and gastric metaplasia were seen in further 34% of patients with duodenal biopsies. Granulomas were detected in 14% of gastric and in 12% of duodenal mucosal samples. Helicobacter pylori infection affected 35% of patients with gastric biopsies, 24% of those with active focal gastritis, and was found in 7/10 foci of gastric metaplasia in the duodenum. Normal gastric mucosa was present in 11% and normal duodenal mucosa in 12% of patients. In our opinion irregularly distributed foci of inflammatory lesions with crypt abscesses, focal fibrosis and/or lymphoid tissue proliferation in the lamina propria of gastroduodenal biopsies, particularly in the absence of H. pylori infection are most important lesions in the diagnosis of Crohn's disease. Epithelioid granulomas are less common and other aetiologies should be excluded.

Hepatocellular carcinoma in young patients.

The study was based on the biopsy material collected in Eastern coastal region of South Africa with high incidence of primary hepatocellular carcinoma (HCC). Forty-one patients were between 9 and 25 years old of the total number of 474 cases of HCC available for examination. Liver biopsies were fixed in 10% of neutralised formalin, processed to paraffin blocks, cut and stained with hematoxylin and eosin, silver reticulin, Masson trichrome and Prussian blue stains. Representative biopsies of 21 patients younger than 25 years and 56 older than 35 years were in addition examined immunohistochemically with HBsAg antibody, endothelial marker (F VIII-related antigen) and for oncoproteins c-myc and c-erbB-2 using peroxidase-antiperoxidase method. Cirrhotic liver was evident in 41.5% of all patients and in 28% of younger than 25 years. Hemosiderosis of the liver of patients over 35 years was nearly twice as common as in younger than 25 years and showed the opposite relationship to the presence of HBsAg in liver tissue. Oncoprotein expression was also higher in tumor tissue of younger patients. These results indicate the etiological association of HCC with HBV infection, cirrhosis and possibly siderosis of the liver with HCC. Simultaneous expression of oncoproteins and HBsAg indicate the primary importance of viral infection in etiopathogenesis of HCC.

Haemostatic and immunological sequelae of portacaval shunt in rats.

We have evaluated the link between haemostatic abnormalities and immune dysfunction in liver disease by evaluating parameters of cellular and humoral immunity in conjunction with coagulation profiles in rats following portacaval anastomosis, induction of portal hypertension by portal vein stenosis or by sham surgical procedures. Twelve weeks following surgery, portacaval shunted rats were markedly anaemic (8.9 +/- 0.6 g/dl; controls 12.3 +/- 1.4 g/dl, p < 0.05), had low plasma fibrinogen levels (0.6 +/- 0.3 g/l, controls 2.5 +/- 0.2 g/l p < 0.05) and markedly elevated fibrin(ogen) degradation products (FDP) titres (1/40-1/80; controls < 1/10. p < 0.05). Portal vein stenosed rats were less anaemic (11.5 +/- 0.8 g/dl), had near normal fibrinogen levels (2.1 +/- 0.3 g/l) but elevated FDP levels (1/40-1/80). Both portacaval shunted and portal vein stenosed rats had elevated serum IgG levels (35.1 +/- 14.1 g/l; 29.2 +/- 13.9 g/l respectively; control values 20 +/- 5.9 g/l p < 0.05 for comparison with both experimental groups). Intrinsic lymphocyte proliferation to T and B cell mitogens was markedly depressed in the portacaval anastamosed rats when compared to controls. Serum factors inhibitory to control lymphocyte proliferation were noted in the shunted rats. Phagocytosis of complement and immunoglobulin sensitised sheep RBC by Kupffer cells purified from rats that had undergone portacaval shunting was markedly reduced (p < 0.05). The increased degree of phagocytosis following exposure to LPS-endotoxin (50 micrograms/ml) was proportionate in degree to the control group. Spontaneous release of bioactive lymphocyte activating factors (IL-1 and IL-6) by purified rat sinusoidal cell populations was decreased in the portacaval shunted group, and decreased still further following stimulation with LPS (50 micrograms/ml) in vitro. The observation that many of the haemostatic and immunological abnormalities associated with chronic liver disease are present in rats with surgically created portacaval shunts or with induced portal hypertension, lends credence to the hypothesis that shunting of portal blood is, at least in part, responsible for many of the systemic manifestations associated with chronic liver disease.

Hepatocellular carcinoma in young patients: histology, cellular differentiation, HBV infection and oncoprotein p53.

The study of 226 cases of hepatocellular carcinoma (HCC) in a homogenous rural Southern African population is based on the assessment of histology, HBV infection, p53 oncoprotein and transforming growth factor alpha (TGFa) expression. Epidemiological and morphological observations were compared to HCC observed in 89 cases from pathological files in Poland and published information from Japan and Italy. Comparatively high number of young patients with HCC in Africa presented high rates of HBV infection, p53 oncoprotein overexpression and high HBsAg/p53 correlation rates. In all patients histological grading of HCC was inversely related to p53 and TGFa expression. No significant differences in histological grading of HCC and patients' mean age were noted between various population groups. The association of hepatic cirrhosis was at least twice as common in non-African patients, whereas iron overload was noted almost exclusively in African patients livers. Signs of HBV infection were lowest in Japanese female patients. The mechanism by which early HBV infection contributes to hepatocarcinogenesis at an early stage of life is confirmed by epidemiological observations in Poland and by the clear association of p53 gene with HBsAg and the age of patients.

Hematopoietic stem cell markers are expressed by ductal plate and bile duct cells in developing human liver.

The identification of ductal plate cells as likely progenitors for bile duct epithelium and hepatocytes and their possible reappearance as oval cells in the regenerating liver have generated much interest in their pluripotential capacities. We have examined the distribution of three hematopoietic stem cell markers, c-kit, CD34, and CD33 in addition to laminin, the standard cytokeratin markers CAM 5.2, CK 18, and CK 7 and the oval cell marker OV-6 in fetal liver during various stages of development. Hematopoietic stem cell markers were expressed in ductal plate cells in a pattern similar to the early cytokeratin markers CAM 5.2 and CK 18. Cells stained strongly for these early cytokeratin markers until 22 weeks. Thereafter, the expression of these markers decreased while positivity for CK 7 increased. Bile duct cells showed a distribution of hematopoietic and cytokeratin markers resembling that of ductal plate cells. Both ductal plate cells and bile duct cells expressed OV-6 strongly throughout development. This study showed similarity between hepatic and bile duct precursors and bone marrow stem cells. The comparable distribution of markers in bile duct epithelium and ductal plate cells may imply fewer transitional stages between ductal plate cells and bile duct epithelium than between the putative stem cells and hepatocytes.