Histology and histopathology Vol.31,nº 10 (2016)
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- PublicationOpen AccessMesotheliomas show higher hyaluronan positivity around tumor cells than metastatic pulmonary adenocarcinomas(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Törrönen, Kari; Soini, Ylermi; Pääkkö, Paavo; Parkkinen, Jyrki; Sironen, Reijo; Rilla, KirsiHyaluronan is a unique glycosaminoglycan of the extracellular matrix, abundant in normal connective tissues but highly increased in many pathological conditions like cancer. Mesothelioma, one of the most malignant cancer types, is associated with high content of hyaluronan, with elevated levels of hyaluronan in pleural effusions and serum of the patients. Metastatic lung adenocarcinomas are typically less aggressive and have a better prognosis as compared to mesotheliomas, a reason why it is highly important to find reliable tools to differentiate these cancer types. The main purpose of this study was to evaluate the amount of hyaluronan, hyaluronan producing synthases (HAS’s) and hyaluronan receptor CD44, in mesothelioma and metastatic lung adenocarcinomas. Furthermore, we wanted to clarify the role of hyaluronan, CD44 and HAS’s as putative markers for differentiating malignant mesothelioma from metastatic lung adenocarcinomas. The main finding of this study was that mesotheliomas are significantly more positive for hyaluronan staining than metastatic adenocarcinomas. Unexceptionally, a trend of CD44 positivity of stromal cells was higher in adenocarcinomas as compared to mesotheliomas. However, no statistically significant differences were found between the staining of any of the HAS isoenzymes either in tumor cells or stromal cells of different groups of cases. The results show that there are significant differences in hyaluronan content between metastatic lung adenocarcinomas and mesotheliomas. However, as previous studies have suggested, hyaluronan alone is not a sufficient independent marker for diagnostic differentiation of these cancer types, but could be utilized as a combination together with other specific markers.
- PublicationOpen AccessAbundant lubricin expression suggests a link between synoviocytes, synovial tumors, and myxomas(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Solka, Kathryn A.; Schmid, Thomas M.; Miller, Ira J.Progenitor cell differentiation into fibroblastlike synoviocytes (FLSs) and their ensuing phenotypic changes are incompletely explored. Synovial lining is composed of intimal macrophages and FLSs. FLSs have epithelioid morphology and directionally secrete components of synovial fluid, including lubricin. We stained human tissues and tumors using two anti-lubricin antibodies. Lubricin was found in FLSs in synovium and in tenosynovial giant cell tumors (TSGCTs) and not in the associated monocyte/macrophage cells, which were identified by double immunostaining for CD163. In TSGCTs, giant cells, known to form by fusion of mononuclear cells, were negative for both lubricin and CD163. Occasional mononuclear cells with the same phenotype were also seen, suggesting that the precursors of the giant cells are derived from the minor CD163- negative monocyte subset. Lubricin was also detected in intramuscular myxomas, in early myxoid changes of ganglion cysts, and in one of five low-grade myxofibrosarcomas, but not in other fibroconnective tissues, epithelial tissues, or other tumors tested. This suggests that lubricin expression may typify adaptive and neoplastic changes along a pathway toward FLSs. Further support for this concept comes from ganglion cysts and juxta-articular myxoma tumors, which show a spectrum of myxoid, cystic and synovial differentiation, and in which moderate lubricin staining of myxoid stroma was seen.
- PublicationOpen AccessEthanol-induced mitophagy in liver is associated with activation of the PINK1-Parkin pathway triggered by oxidative DNA damage(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Eid, Nabil; Ito, Yuko; Horibe, Akio; Otsuki, YoshinoriMitophagy is a cytoprotective mechanism against mitochondrial damaging agents. Studies demonstrating morphological evidence for the involvement of the PINK1-Parkin pathway in the hepatocyte mitophagic response to ethanol toxicity, and potential links to apoptosis and mitochondrial alterations such as spheroid formation are still lacking. We addressed these unresolved issues using a rat model of binge alcohol exposure. Adult rats were injected with ethanol (5g/kg) and liver samples were taken at 0, 3, 6, and 24 hours after ethanol administration and processed for light and electron microscopic studies. Ethanol induced a low level of hepatocyte apoptosis, peaking at 3 h and decreasing significantly by 24 h. In contrast, there was enhanced formation of mitophagic vacuoles in the majority of normal hepatocytes of ethanol-treated rats (ETRs), which peaked at 6 h and was maintained up to 24 h based on electron microscopy and TUNEL/LC3 double labelling. Moreover, enhanced mitophagy in ETR hepatocytes was confirmed by increased LC3 puncta formation, and co-localization of Parkin and LC3 with mitochondrial and lysosomal markers. Immunoelectron microscopy demonstrated the localization of PINK1 and Parkin to damaged mitochondria of ETR hepatocytes, which was consistent with co-localization of Parkin with 8-OHdG, a marker of oxidative mitochondrial DNA damage. Furthermore, electron microscopy showed enhanced formation of mitochondrial spheroids in ETR hepatocytes. These data are the first direct morphological evidence linking PINK1-Parkin pathway activation to the enhanced mitophagic response of hepatocytes to ethanol toxicity. Ethanol-induced hepatic mitophagy may be a prosurvival mechanism, which may have therapeutic implications.
- PublicationOpen AccessAtrophic hepatocytes express keratin 7 in ischemia-associated liver lesions(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Delladetsima, Ioanna; Sakellariou, Stratigoula; Kokkori, Aikaterini; Tiniakos, DinaAim: To investigate atrophic parenchymal changes in ischemic liver conditions. Design: We studied 18 cases of hepatic lesions with atrophic changes due to altered blood flow (hepatic venous congestion n=15 including 4 cases with additional nodular regenerative hyperplasia-NRH, NRH n=1, and antiphospholipid syndrome with patchy parenchymal atrophy n=2). Metaplastic hepatocellular changes, hepatocyte proliferation, hepatic stellate cell (HSC) activation, and sinusoidal capillarization were examined immunohistochemically with antibodies to keratins (K) 7 and 19, Ki67, αSMA and CD34, respectively. Results: K7 was positive and K19 was negative in zone 3 atrophic hepatocytes in venous congestion and in areas of plate atrophy, as well as in congested or compressed sites in NRH. Sinusoidal CD34-positivity indicating capillarization accompanied K7 immunoexpression. Masson trichrome revealed sinusoidal fibrosis to be restricted in atrophic areas, usually mild and in 7 cases focally dense. αSMA expression expanded beyond K7- positive areas. Ki67 was negative in K7-positive hepatocytes. Conclusion: Ischemic parenchymal changes are characterized by hepatocyte K7 immunoexpression, sinusoidal capillarization, HSC activation and lack of cellular proliferation, indicating an early reaction of the major liver parenchyma cellular components creating a more resistant microenvironment. These phenotypic alterations may prove valuable in the discrimination of ischemic liver lesions.
- PublicationOpen AccessRelationships between variable time, percentage of food restriction and liver histology: which alternative is the best for non-alcoholic fatty liver disease (NAFLD) prevention?(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Makovicky, Peter; Tumova, Eva; Volek, Zdenek; Makovicky, Pavol; Sedlacek, RadislavThe objective of this study was to analyse the hepatic effects of food restriction in an experimental rabbit model. The study comprised 105 rabbits divided into 6 groups. The two control groups were fed ad libitum (ADL) during the entire experiment (C1 and C2). The experimental groups were restricted between 42-49 days of age, where the rabbits received 50g (R1) or 65g (R2) of food per rabbit per day. Others were restricted between 35-42 days of age, where the rabbits received 50g (R3) or 65g (R4) of food per rabbit per day. For liver analysis, 5 rabbits per group were slaughtered at the ages of 49, 56, 63, 70 days from the R1, R2 groups and at 42, 49, 70 days from the R3, R4 groups. All animals from the C1 and C2 groups developed steatosis with inflammation. Animals from the R1 and R2 groups developed steatosis without inflammation while in the R3 and R4 groups steatosis was not visible. In C1 and C2 groups we observed mostly fatty deposit accumulations while in the R1, R2, R3 and R4 groups, more PAS-positive material accumulations were visible. Liver steatosis correlated with inflammation development and interstitial tissue growth. These results can be used in clinical praxis as signs of NAFLD progression. Early food restriction had intense effects on liver morphology and it seems promising that similar approaches could be applied as preventive treatment for NAFLD development.