Immunohistochemical detection of polyductin and co-localization with liver progenitor cell markers during normal and abnormal development of the intrahepatic biliary system and in adult hepatobiliary carcinomas.

The longest open reading frame of PKHD1 (polycystic kidney and hepatic disease 1), the autosomal recessive polycystic kidney disease (ARPKD) gene, encodes a single-pass, integral membrane protein named polyductin or fibrocystin. A fusion protein comprising its intracellular C-terminus, FP2, was previously used to raise a polyclonal antiserum shown to detect polyductin in several human tissues, including liver. In the current study, we aimed to investigate by immunohistochemistry the detailed polyductin localization pattern in normal (ductal plate [DP], remodelling ductal plate [RDP], remodelled bile ducts) and abnormal development of the primitive intrahepatic biliary system, known as ductal plate malformation (DPM).

Bile duct to portal space ratio and ductal plate remnants in liver disease of infants aged less than 1 year.

Aim: To validate the bile duct to portal space ratio as an independent factor useful for the prognosis of neonatal liver disease.

Methods: We assessed the maturation of the intrahepatic bile duct system (IBDS) in 87 consecutive infants aged less than 1 year undergoing non-subcapsular, adequate (at least six portal tracts), liver needle biopsies because of hepatomegaly and/or cholestasis. The maturation of the IBDS was evaluated by immunohistochemistry with an antibody directed to cytokeratin 7 (CK7), a biliary-type intermediate filament of the cytoskeleton, and a schema showing the IBDS remodelling.

Chromosomal imbalances in sporadic neuroendocrine tumours of the thymus.

Neuroendocrine (carcinoid) tumours of the thymus are rare neoplasms characterized by a highly malignant clinical behavior. Some of these tumors are associated with MEN1. In this study we evaluated 10 cases of sporadic thymic neuroendocrine tumours using immunohistochemistry and comparative genomic hybridization (CGH).

Cystic thymoma.

Thymic cysts are rare lesions located along the anatomical course of the third pharyngeal pouch. While most of the cases represent congenital cysts, they may also be related to neoplasms. We report a case of a micronodular thymoma with lymphoid stroma, which was completely built of small cysts, discuss the pathologic features of this tumor type and review the etiology and other aspects of thymic cysts.

Oncogenetic tree models based on cytogenetic data: new insights into the development of epithelial tumors of the thymus.

Epithelial tumors of the thymus are rare neoplasms typically arising in the anterior mediastinum. There is an ongoing discussion whether thymomas of different histological subtypes form a biological continuum or represent distinct biological entities. To further investigate this question, we performed a statistical analysis of CGH data of 65 previously published cases.

Immunohistochemical and cytogenetic characterization of acantholytic squamous cell carcinoma of the breast.

Primary acantholytic squamous cell carcinoma (ASCC) of the breast is a rare and aggressive variant of invasive breast cancer. Here we report two new cases of ASCC and their immunohistochemical and cytogenetic characterization. One case was associated with systemic metastases and death and the other with local failure prior to loss of follow-up.

BRAF mutations distinguish anorectal from cutaneous melanoma at the molecular level.

Background & Aims: Anorectal melanoma (AM) is a rare but highly malignant tumor, displaying histologic and immunohistochemical features very similar to cutaneous melanoma (CM). Because BRAF mutations were recently identified in the majority of CM and nevi, we investigated AM for BRAF mutations and mutations of NRAS , an additional component of the MAPK-signalling pathway.

Methods: DNA from formalin-fixed and paraffin-embedded AM was PCR amplified and sequenced.

Wnt-signaling and apoptosis after neoadjuvant short-term radiotherapy for rectal cancer.

Recent surgical concepts for primary rectal cancer include the combination of surgery and short-term neoadjuvant radiotherapy (STNR). This is usually given in a dose of 25 Gy over five days in order to reduce local recurrence rates. Clinical studies have shown that local recurrence is found in some patients despite STNR.

Analysis of somatic APC mutations in rare extracolonic tumors of patients with familial adenomatous polyposis coli.

Patients with familial adenomatous polyposis coli (FAP) carry heterozygous mutations of the APC gene. At a young age, these patients develop multiple colorectal adenomas that consistently display a second somatic mutation in the remaining APC wild-type allele. Inactivation of APC leads to impaired degradation of beta-catenin, thereby promoting continuous cell-cycle progression.

Expression of cell cycle-related gene products in different forms of primary versus recurrent PVNS.

Expression patterns of cell cycle regulating gene products and Ki-67 in proliferating synovial cells of primary and recurrent pigmented villonodular synovitis (PVNS) in localized and diffuse lesions were examined by immunohistochemistry. Alterations of cell cycle-related proteins were seen in 98.7% of analyzed lesions.

Loss of SMAD4 function in small intestinal adenocarcinomas: comparison of genetic and immunohistochemical findings.

Despite morphological similarities between adenocarcinomas of the small and the large intestine, recent evidence suggests that both tumor types follow different genetic pathways. In particular, inactivation of the APC tumor suppressor gene, a characteristic alteration of colorectal carcinomas, does not seem to play a significant role in sporadic small intestinal tumorigenesis. We could recently show that inactivating mutations of the SMAD4 gene frequently occur in small intestinal adenocarcinomas.

Differential diagnosis of non-epithelial tumors of the pancreas: malignant non-epithelial pancreatic tumor with focal pigmentation.

Non-epithelial tumors only rarely affect the pancreas. In this report, we describe a malignant non-epithelial tumor with combined characteristics of malignant peripheral nerve sheath tumor (MPNST) and malignant melanoma. To more closely define the differential diagnosis of MPNST with focal pigmentation versus metastatic melanoma resembling MPNST, the tumor was investigated using histomorphology, immunohistochemistry, electron microscopy, and comparative genomic hybridization.

Microcystic tubulopapillary carcinoma of the pancreas: a new tumor entity?

An unusual pancreatic tumor with microcystic and tubulopapillary features was observed in a 53-year-old woman. The tumor presented as a large, focally cystic mass in the head of the pancreas, which compressed the surrounding structures. The histological and immunohistochemical analysis revealed a neoplasm that could not be assigned to any of the known pancreatic tumor types.

Expression of acyl-CoA synthetase 5 reflects the state of villus architecture in human small intestine.

Several disorders of the small intestine are associated with disturbances in villus architecture. Thus, an understanding of the molecular mechanisms associated with the differentiation of villi represents an important step in the improvement of the understanding of small intestinal pathology. Screening of antibodies from a hybridoma library led to the identification of an acyl-CoA synthetase 5-specific monoclonal antibody.

Carcinogen inducibility in vivo and down-regulation of DMBT1 during breast carcinogenesis.

Deleted in malignant brain tumors 1 (DMBT1) has been proposed as a candidate tumor suppressor for brain and epithelial cancer. Initial studies suggested loss of expression rather than mutation as the predominant mode of DMBT1 inactivation. However, in situ studies in lung cancer demonstrated highly sophisticated changes of DMBT1 expression and localization, pointing to a chronological order of events.

Oligoclonal T-cell populations in an inflammatory pseudotumor of the pancreas possibly related to autoimmune pancreatitis: an immunohistochemical and molecular analysis.

Inflammatory pseudotumors (IPT), also known as inflammatory myofibroblastic tumors (IMT), are benign inflammatory processes that may have an infectious etiology and are very rare in the pancreatico-biliary region. Recent studies suggest a biological distinction between IPT and IMT, the latter being a true neoplastic process. We describe a case of pancreatic IPT, originally diagnosed as malignancy, which presumably recurred 4 months after the operation.

The role of platelet derived growth factor in endomyocardial biopsies shortly after heart transplantation in relation to postoperative course.

Objective: Platelet-derived growth factor (PDGF) plays an important role in structural alterations of blood vessels after heart transplantation (HTx). The aim of this study was to clarify the effect of peritransplant injury and postoperative complications on the expression of PDGF ligand and receptor.

Methods: Right ventricular endomyocardial biopsies were collected from 46 patients before implantation, and then 1 and 2 weeks after HTx.

Impaired expression of acyl-CoA-synthetase 5 in epithelial tumors of the small intestine.

Fatty acids are implicated in tumorigenesis, but data are limited concerning endogenous fatty acid metabolism of tumor cells in adenomas and adenocarcinomas of the small intestine. The recently cloned human acyl-CoA-synthetase 5 (ACS5) is predominantly found in the small intestine and represents a key enzyme in providing cytosolic acyl-CoA thioesters. Protein synthesis and mRNA expression of ACS5 were studied in human intestinal tissues using different methods, including a newly established monoclonal antibody.

CTCF gene mutations in invasive ductal breast cancer.

The CTCF gene encodes for a transcriptional repressor of the c-myc oncogene and has previously been mapped to one of the smallest regions of overlapping interstitial deletions on chromosome 16q22.1 in invasive breast cancer. This chromosomal region is frequently deleted in both invasive lobular and ductal breast carcinomas.

Somatic mutations in familial adenomatous polyps. Nuclear translocation of beta-catenin requires more than biallelic APC inactivation.

Germline mutations of the APC gene cause familial adenomatous polyposis coli (FAP). APC inactivation results in dysregulation of wnt/wingless signaling and contributes to chromosomal instability in vitro. To investigate somatic alterations that follow a known germline mutation and contribute to the transition from normal to neoplastic mucosa, we studied 10 adenomatous polyps from a 27-year-old patient with an APC germline mutation at codon 554.

Clusters of chromosomal imbalances in thymic epithelial tumours are associated with the WHO classification and the staging system according to Masaoka.

Using comparative genomic hybridisation, we investigated chromosomal imbalances in 28 cases of thymic epithelial neoplasms including type A, B2, B3, the A component of type AB and different subtypes of type C thymoma. To identify different patterns of chromosomal aberrations associated with the biological behaviour and the histological diversity of thymomas, a hierarchical cluster analysis of 65 cases was performed. The here-reported Comparative Genomic Hybridisation (CGH) data (28 cases) of partly uninvestigated tumour subtypes were pooled with previously published data of chromosomal imbalances of 37 thymomas (Zettl et al.

Flow cytometric detection of spontaneous apoptosis in human breast cancer using the TUNEL-technique.

Microscopic detection of structural alterations is the most reliable method to identify apoptotic cells, which however, does not allow any correlation with cell cycle phases. Discrimination of individual cells within solid human tumors undergoing apoptotic death is possible by flow cytometry where apoptotic cells appear in a hypodiploid sub G0/1-peak as a consequence of partial DNA loss. To refer induction of apoptosis to cell cycle phases we adopted the terminal deoxynucleotidyl transferase nick-end-labelling (TUNEL) technique to flow cytometry which enables the detection of cellular DNA content and DNA fragmentation by multiparametric analysis.

Frequent downregulation of DMBT1 and galectin-3 in epithelial skin cancer.

DMBT1 and galectin-3 are potential interacting proteins with presumably complex roles in tumorigenesis. While at present a variety of mechanisms are discussed for DMBT1 and its participation in cancer, galectin-3 is commonly known to exert tumor-promoting effects. However, in vitro studies in a rodent system have suggested that DMBT1/galectin-3 interaction in the ECM triggers epithelial differentiation, which would point to tumor-suppressive properties.

Expression of calnexin reflects paneth cell differentiation and function.

It has been suggested that the behavior and function of Paneth cells in metaplasia are different from those found in normal intestinal mucosa. In this study, we investigated whether calnexin, a protein involved in secretory pathways, might be associated with differentiation and function of Paneth cells in normal small intestine, in complete intestinal metaplasia of the stomach, and in Paneth cell-rich adenomas. Differentiation and function of Paneth cells was monitored by Ki67, lysozyme, and morphologic features.

Cytokine/chemokine messenger-RNA expression profiles in ulcerative colitis and Crohn's disease.

To define mediator profiles in inflamed and noninflamed areas in inflammatory bowel disease (IBD) we analyzed the expression of 35 messenger-RNAs (mRNAs) encoding cytokines, chemokines, and some related molecules in transmural gut tissues (n=138) from patients with ulcerative colitis (UC), Crohn's disease (CD), and inflammatory and normal controls by real-time quantitative reverse transcription polymerase chain reaction. Using sample collectives with a comparable degree of inflammation, most parameters investigated showed similarly increased mRNA expression levels in both active UC and CD. This included proinflammatory cytokines, but also interferon (IFN) gamma and several IFN-gamma inducible chemokines.