Claudin-7 protein differentiates canine cholangiocarcinoma from hepatocellular carcinoma

The aim of the present study was to characterise the expression pattern of claudin-7 tight junction protein in canine normal liver, hyperplastic and primary neoplastic lesions of the canine liver and whether this tight junction protein can help differentiate canine cholangiocarcinomas from canine hepatocellular carcinomas. Methods and results: Necropsy samples included 15 canine normal liver tissue samples, 10 hepatocellular nodular hyperplasias, 6 hepatocellular adenomas, 15 well-differentiated and 6 poorly differentiated hepatocellular carcinomas, 6 cholangiocellular hyperplasias, 10 cholangiocellular adenomas, 15 well-differentiated and 6 poorly differentiated cholangiocarcinomas, 6 normal extrahepatic bile ducts, 8 normal gall bladder tissue samples, and 5 cystic mucinous hyperplasias of the gall bladder. In all canine normal liver tissue samples the hepatocytes were negative for claudin-7 and the normal biliary epithelial cells showed intense basolateral membrane claudin-7 positivity. In all cholangiocellular hyperplasia samples and in all cholangiocellular adenoma samples the benign cholangiocytes showed intense basolateral membrane positivity for claudin-7. In all samples of the well-differentiated and poorly differentiated cholangiocarcinomas, the malignant neoplastic biliary epithelial cells showed intense basolateral membrane positivity for claudin-7. Neither the hyperplastic nodules of the liver cells nor the hepatocellular adenomas reacted with claudin-7. The well-differentiated and poorly differentiated hepatocellular cancers were negative for claudin-7. The epithelial cells of canine normal extrahepatic bile ducts, gall bladder and cystic mucinous hyperplasias of the gall bladder showed intense basolateral membrane positivity for claudin-7. Differences in the intensity of claudin-7 reaction were not apparent among different types of proliferative lesions of cholangiocytes or degrees of cellular differentiation of neoplastic biliary epithelial cells. Conclusion: Consequently, we hypothesize that claudin-7 is an excellent immunohistochemical marker of the cholangiocellular differentiation in canines and can be used to detect benign and malignant proliferative lesions of the canine biliary tract. It can also help to differentiate canine cholangiocarcinomas from hepatocellular carcinomas

Enhancer of zeste homologue 2 (EZH2) is a reliable immunohistochemical marker to differentiate malignant and benign hepatic tumors

BACKGROUND: The immunohistochemical demonstration of Enhancer of zeste homologue 2 (EZH2) proved to be a useful marker in several tumor types. It has been described to distinguish reliably hepatocellular carcinomas from liver adenomas and other benign hepatocellular lesions. However, no other types of malignant liver tumors were studied so far. METHODS: To evaluate the diagnostic value of this protein in hepatic tumors we have investigated the presence of EZH2 by immunohistochemistry in hepatocellular carcinomas and other common hepatic tumors.EZH2 expression was examined in 44 hepatocellular carcinomas, 23 cholangiocarcinomas, 31 hepatoblastomas, 16 other childhood tumor types (rhabdomyosarcoma, neuroblastoma, Wilms' tumor and rhabdoid tumor), 17 metastatic liver tumors 24 hepatocellular adenomas, 15 high grade dysplastic nodules, 3 biliary cystadenomas, 3 biliary hamartomas and 3 Caroli's diseases. RESULTS: Most of the malignant liver tumors were positive for EZH2, but neither of the adenomas, cirrhotic/dysplastic nodules, reactive and hamartomatous biliary ductules stained positively. CONCLUSIONS: Our immunostainings confirm that EZH2 is a sensitive marker of hepatocellular carcinoma, but its specificity is very low, since almost all the investigated malignant liver tumors were positive regardless of their histogenesis. Based on these results EZH2 is a sensitive marker of malignancy in hepatic tumors. In routine surgical pathology EZH2 could be most helpful to diagnose cholangiocarcinomas, because as far as we know this is the first marker to distinguish transformed and reactive biliary structures. Although hepatoblastomas also express EZH2, the diagnostic significance of this observation seems to be quite limited whereas, the structurally similar, other blastic childhood tumors are also positive. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1173195902735693

V-shaped inversion domains in InN grown on c-plane sapphire

Inversion domains with a V-shape were found to nucleate inside a Mg-doped InN heteroepitaxial layer. They resemble Al-polarity domains, observed recently, in N-polarity AlN films. However, the angle between the side-walls of the V-shaped domain and the c-axis differs in these two cases. In InN, this angle is almost two times bigger than that reported for AlN. The origin of V-shaped inversion domains in InN film is not yet clear

InN Nanorods and Epi-layers: Similarities and Differences

Transmission electron microscopy was applied to study InN nanorods grown on the a-, c-and r-plane of Al{sub 2}O{sub 3}, and (111) Si substrates by non-catalytic, template-free hydride metal-organic vapor phase epitaxy (H-MOVPE). Single crystal nanorod growth was obtained on all substrates. However, the shape of the nanorods varied depending on the substrate used. For example, nanorods grown on r-plane sapphire and (111) Si have sharp tips. In contrast, growth on a- and c- planes of Al{sub 2}O{sub 3} results in flat tips with clear facets on their sides. The structural quality of these nanorods and their growth polarity are compared to crystalline quality, surface roughness, defects and growth polarity of InN layers grown by MBE on the same planes of Al{sub 2}O{sub 3}

Topological Phase Diagram of a Two-Subband Electron System

We present a phase diagram for a two-dimensional electron system with two populated subbands. Using a gated GaAs/AlGaAs single quantum well, we have mapped out the phases of various quantum Hall states in the density-magnetic filed plane. The experimental phase diagram shows a very different topology from the conventional Landau fan diagram. We find regions of negative differential Hall resistance which are interpreted as preliminary evidence of the long sought reentrant quantum Hall transitions. We discuss the origins of the anomalous topology and the negative differential Hall resistance in terms of the Landau level and subband mixing.Comment: 4 pages, 4 figure

Compositional Modulation in InxGa1-xN

Transmission Electron Microscopy and x-ray diffraction were used to study compositional modulation in In{sub x}Ga{sub 1-x} N layers grown with compositions close to the miscibility gap. The samples (0.34 < x < 0.8) were deposited by molecular beam epitaxy using either a 200-nm-thick AlN or GaN buffer layer grown on a sapphire substrate. In the TEM imaging mode this modulation is seen as black/white fringes which can be considered as self-assembled thin quantum wells. Periodic compositional modulation leads to extra electron diffraction spots and satellite reflections in x-ray diffraction in the {theta}-2{theta} coupled geometry. The modulation period was determined using both methods. Larger modulation periods were observed for layers with higher In content and for those having larger mismatch with the underlying AlN buffer layer. Compositional modulation was not observed for a sample with x = 0.34 grown on a GaN buffer layer. Modulated films tend to have large 'Stokes shifts' between their absorption edge and photoluminescence peak

Multi-Institutional Datasets Validate the Recursive Partitioning Analysis for Overall Survival in Patients Undergoing Spine Radiosurgery for Spine Metastasis

Purpose/Objective(s): The recently published spine radiosurgery (sSRS) recursive partitioning analysis (RPA) for overall survival (OS) separated patients into 3 distinct prognostic groups. We sought to externally validate this RPA using a multi-institutional dataset. Materials/Methods: A total of 444 patients were utilized to develop the recently published sSRS RPA predictive of OS in patients with spine metastases. The RPA identified three distinct prognostic classes. RPA Class 1 was defined as KPS \u3e70 and controlled systemic disease (n=142); RPA Class 2 was defined as KPS\u3e70 with uncontrolled systemic disease or KPS ≤70, age ≥54 and absence of visceral metastases (n=207); RPA Class 3 was defined as KPS ≤70 and age \u3c54 years or KPS≤70, age ≥54 years and presence of visceral metastases (n=95). We utilized data from large tertiary care centers to validate this RPA. A total of 749 patients were in the validation cohort and were divided based on their RPA Class. Kaplan-Meier method was used to estimate OS and log-rank test was used to compare OS between RPA classes. Results: In the validation cohort (749 patients), the median OS was 11.0 months. One-hundred-thirteen (15.1%) patients were in RPA Class 1, 432 (57.7%) patients in RPA Class 2 and 204 (27.2%) patients in RPA Class 3. The median OS in the validation cohort based on RPA Class was 27.1 months for Class 1, 13.0 months for Class 2 and 3.5 months for Class 3. Patients in RPA Class 1 had a significantly better OS compared to those in Class 2 of the validation cohort (p\u3c0.01). Similarly, patients in RPA Class 2 had a significantly better OS compared to those in Class 3 (p\u3c0.01). Conclusion: The external datasets from two large centers validated the spine SRS RPA successfully for RPA for OS for patients undergoing sSRS for spinal metastases. This is the first RPA for OS to have been externally validated using a large dataset. Based on this validation, upfront spine SRS is strongly supported for patients in RPA Class 1. Upfront SRS is also supported for RPA Class 2 patients. Patients in RPA Class 3 would benefit most from upfront conventional radiotherapy given their poor expected survival. Given successful external validation, this RPA helps guide physicians to identify those patients with spinal metastases who most benefit from sSRS

Free-carrier absorption in Be-and C-doped GaAs epilayers and far infrared detector applications

Far infrared ͑FIR͒ absorption, reflection, and transmission in heavily doped p-GaAs multilayer structures have been measured for wavelengths 20-200 m and compared with the calculated results. Both Be ͑in the range 3ϫ10 18 -2.6ϫ10 19 cm Ϫ3 ͒ and C (1.8ϫ10 18 -4.7ϫ10 19 cm Ϫ3 )-doped structures were studied. It is found that the observed absorption, reflection, and transmission are explained correctly by the model with a dominant role of free-carrier absorption in highly doped regions. High reflection from heavily doped thick layers is attractive for the resonant cavity enhanced FIR detectors