Eszter Turányi

Delta-like protein (DLK) is a novel immunohistochemical marker for human hepatoblastomas

Delta-like protein (DLK) is a membrane protein with mostly unknown function. It is expressed by several embryonic tissues among others by the hepatoblasts of rodent and human fetal livers. We have investigated in the present study if this protein is expressed in human hepatoblastomas. The presence of DLK has been studied by standard immunohistochemistry in 31 hepatoblastomas and in several differential diagnostically related tumours: hepatocellular carcinomas and in undifferentiated childhood neoplasms. All the hepatoblastomas were positive for DLK; the surrounding liver tissue remained negative. The reaction was present in the epithelial component of the tumours. The staining pattern was mostly membranous, occasionally cytoplasmic. The other studied tumours were negative for DLK, except one hepatocellular carcinoma and the differentiating cells of two ganglioneuroblastomas. Therefore, DLK seems to be a highly sensitive and specific marker for hepatoblastomas.

Immunohistochemical classification of ductular reactions in human liver

Turányi E, Dezsö K, Csomor J, Schaff Z, Paku S & Nagy P
(2010) Histopathology 57, 607–614
Immunohistochemical classification of ductular reactions in human liver

Expression of proliferation markers Ki67, cyclin A, geminin and aurora-kinase A in primary breast carcinomas and corresponding distant metastases

Aims To assess the expression of the following cell cycle regulatory proteins in primary metastatic breast carcinomas (MBCs) and on availability in matched distant metastases (DMs): Ki67, cyclin A, geminin and aurora-kinase A (aurkA); and to compare the expression of these markers in early MBC (EMBC) and late MBC separated into groups according to median time point on metastatic event occurred (28 months). Methods The expression of the above mentioned markers was analysed in a total of 47 primary MBCs and 59 DMs (out of which 37 were pairs) by immunohistochemistry. Fourteen breast carcinomas with no relapse over a 10-year follow-up period were utilised as control cases (CBC). Results Among the MBCs, 22 metastasised to the bone, 4 to the lung and 21 to the central nervous system (CNS). Geminin (p<0.001) and Ki67 (p=0.001) were increased in the MBCs while aurkA and cyclin A showed no difference when compared with CBCs. There were no differences between aurkA, cyclin A and geminin expression in MBCs and DMs in general. Expression of Ki67 was, however, elevated (p=0.027) in DMs. In CNS metastases all markers showed elevated expression as compared to MBCs. In bone metastases, geminin was lower (p<0.001) compared with primary MBCs. In the metastases of the lung, the evaluated markers did not show different expression. According to the median follow-up until the metastatic event, Ki67 was found to be significantly elevated in EMBC (p=0.018). Conclusions Ki67 index and geminin distinguish a fraction of MBC with worse prognosis, showing increased levels in the latter in comparison to CBC being tumour-free over a 10-year follow-up period. Ki67 could possibly identify a group of MBCs that develop early DMs.

Leukoencephalopathy, cerebral calcifications and cysts: A family study

We present a clinical, neuro-radiological and genetic study on a family with members suffering from an autosomal dominantly inherited syndrome characterised by epilepsy, cerebral calcifications and cysts, bone abnormalities; progressive neuro-cognitive deterioration and paranasal sinusitis. This syndrome shares several features with leukoencephalopathy with calcifications and cysts also called Labrune syndrome and the condition of cerebroretinal microangiopathy with calcifications and cysts (CRMCC; Coats plus syndrome). Genetic studies in this family did not reveal mutations in the CTC1 gene defected in CRMCC. We interpret our results as those supporting recent findings that despite clinical similarities, late-onset Labrune and Coats plus syndrome might be distinct entities. This family may have Labrune syndrome or a yet unclassified entity; exploration of similar cases could help classifying this one, and related conditions.

DLK is a novel immunohistochemical marker for adrenal gland tumors

Delta-like protein (DLK) is expressed in fetal and adult adrenal glands. We have investigated if this expression is maintained in adrenal gland-derived tumors. All the studied 37 cortical tumors, including five carcinomas, stained positively as well as the 13 examined pheochromocytomas. Thus, DLK is a very sensitive marker for adrenal tumors of cortical and medullary origin. Renal cell carcinomas, presenting the major differential diagnostic problem for cortical tumors, were all negative, as well as melanomas, which are similar to high portion of adrenocortical tumors that react with melan-A. However, all paragangliomas, some carcinoids, and thyroid medullary carcinomas were also positive for DLK. Therefore, this novel immunohistochemical marker seems useful for the identification of adrenocortical tumors while it has limited value for the distinction of pheochromocytomas from diagnostically related neuroendocrine tumors.

Comparison of Predictive Immunohistochemical Marker Expression of Primary Breast Cancer and Paired Distant Metastasis using Surgical Material: A Practice-Based Study

Parallel studies of primary breast carcinomas and corresponding distant metastases samples reveal considerable differences. Our aim was to highlight this issue from another perspective and provide further data based on 98 patient samples: 69 primary breast carcinoma and 85 distant metastases from bone, central nervous system (CNS) and lung (56 paired). Two independent series of immunohistochemical reactions with different antibodies for estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (Her2), along with HER2 fluroscence in situ hybridization (FISH) were performed on tissue microarrays to classify breast carcinoma and distant metastases samples into Luminal A, Luminal B-proliferating, Luminal B-HER2+, HER2+ and triple negative (TNBC) surrogate breast cancer groups. Correlation and agreement between the two assessments of ER and PgR were fair-to-moderate, and almost perfect for HER2 and Ki67. There was 40% discordance concerning immunophenotype between breast carcinomas and distant metastases. Most common metastatic site of ER+ breast carcinoma was the skeletal system (59.2%), whereas that of TNBCs was the CNS (58.8%) and lungs (23.5%). Distant metastases in bones were mostly luminal (54.3%), in the CNS, Luminal B (53.2%), and in the lung, TNBC (37.5%). The change of drugable properties of primary breast cancers in the respective bone and CNS metastases suggests that characterization of the metastasis is necessary for appropriate treatment planning.

Architectural and Immunohistochemical Characterization of Biliary Ductules in Normal Human Liver

The canals of Hering or biliary ductules have been described to connect the bile canaliculi with the interlobular bile ducts, and thus forming the distal part of the biliary tree. Studies in the last two decades suggested that the cells constructing these ductules could behave as hepatic progenitor cells. The canals of Hering are confined to the periportal space in the rat, while they have been reported to spread beyond the limiting plate in human liver. The distribution of the distal biliary ductules in normal human hepatic tissue has been investigated in our recent experiments. We could demonstrate the presence of interlobular connective tissue septa in a rudimentary form in healthy livers. The canals of Hering run in these septa in line with the terminal branches of the portal vein and hepatic arteries. This arrangement develops in the postnatal period but regresses after early childhood. The canals of Hering can be identified by the unique epithelial membrane antigen (EMA)-/CD56+/CD133+ immunophenotype. The canals of Hering leave the periportal space and spread into the liver parenchyma along rudimentary interlobular septa outlining the hepatic lobules. Our observations refine the original architectural description of the intraparenchymal portion of the canals of Hering in the human liver. The distinct immunophenotype supports their unique biological function.

1,4‐Bis[2‐(3,5‐dichloropyridyloxy)]benzene induces substantial hyperplasia in fibrotic mouse liver

The proliferative response of hepatocytes in vivo can be induced by two mechanisms: severe damage to hepatic tissue results in regenerative growth and so‐called primary hepatocyte mitogens can initiate liver cell proliferation without preceding loss of parenchyma. The regulation of the two responses is quite different. The decreased regenerative response of cirrhotic/fibrotic liver is well known, and is a severe obstacle to surgery of the diseased liver. In the present experiments we investigated the efficiency of a primary hepatocyte mitogen 1,4‐Bis[2‐(3,5‐dichloropyridyloxy)]benzene (TCPOBOB) on two different liver cirrhosis/fibrosis models in mice induced by chronic administration of CCl4 and thioacetamide respectively. BrdU incorporation and cyclin A expression established clearly that there is a reduced but still powerful mitogenic response of the fibrotic livers. Therefore, primary hepatocyte mitogens appear to be suitable to be used to rescue the regenerative response of cirrhotic livers.

Atypical teratoid/rhabdoid tumor arising in a malignant glioma

Atypical teratoid/rhabdoid tumor (AT/RT), a highly malignant brain tumor in young children, usually arises de novo and has only rarely been described as a secondary malignancy. Here, we present a case of a child with glioblastoma, who was treated postoperatively by a combination of temozolomide, irradiation, and bevacizumab. AT/RT was diagnosed as a secondary tumor, 2.5 years following primary diagnosis. The child died 13 months after the diagnosis of AT/RT. This case demonstrates that malignant gliomas may give rise to AT/RT. It also emphasizes the diagnostic value of a repeated tumor biopsy in the recurrence setting.

Extranodal marginal zone lymphoma of the CNS arising after a long-standing history of atypical white matter disease

In February 2009 a 39 year old female patient with a long standng history of atypical white matter lesions mimicking multiple clerosis was admitted to the Department of Neurology, Budapest, ue to disease progression. The onset of disease was at the age of 16 with retrobulbar neuitis on the right side. Two years later the neuritis also involved the eft side. Optometric examination showed temporal decoloration f the papilla and optic nerve atrophy on both sides. Brain MR mages were abnormal with confluent high signal intensities in the hite matter of the trigonum on both sides. Although CSF examnation did not detect oligoclonal bands, multiple sclerosis was iagnosed. Control-MRI examination at the age of 28 showed diffuse hyperntensive signals on T2, proton and FLAIR images in the white atter of the right frontal lobe and in both parieto-occipital egions. In addition to atypical multiple sclerosis, leukodystrohy was also considered. Within several years, her visual acuity radually worsened and she became amblyopic. Subsequent MRI erformed at the age of 33, 35 and 37 revealed a slow increase n the intensity of the white matter lesions. At the age of 37 he suffered from a generalized convulsion. From that time she eceived carbamazepin as monotherapy, later combined with valroate and levetiracetam. Due to the slowly progressive diffuse hite matter lesions, retrobulbar neuritis, depression, repeated ertigo and numbness, mitochondrial disease was also discussed. owever, muscle biopsy did not confirm any pathological lesions, urthermore serum ammonia and creatinin kinase levels were ormal. In February 2009 she presented with a visual acuity of 0.15 n the right side and 0.5 on the left side. She exhibited horzontal rotary nystagmus in every position of the bulbs, brisk endon reflexes and dysthymia. Laboratory examinations includng serum lactate, hormones and quantitative immunoglobulines ere normal. Serum immuno-electrophoresis did not detect oligolonal bands. EEG detected rarely theta waves in the temporal egion on the right side. CSF examination showed elevated proein (157 mg/dL) and IgG-levels (8.55 mg/dL) but no increase in hite blood cells. Flow cytometry of CSF, however, detected a Bell population with lambda light chain restriction (kappa:lambda atio 1:4). Brain MRI showed further mild progression of the white mater lesion with inhomogeneous contrast enhancement and marked nhancement along the sulci of the right frontal lobe in T2 weighted mages (Fig. 1A). MR spectroscopy revealed moderately elevated holin levels in the right frontal lobe. A brain biopsy from the ight frontal lobe was performed to clarify these striking radioogic findings. Histology revealed a dense, perivascular accentuated nfiltration of the brain parenchyma by small B-lymphocytes with