Histology and histopathology Vol.29, nº 6 (2014)
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- PublicationOpen AccessGASC1 expression in lung carcinoma is associated with smoking and prognosis of squamous cell carcinoma(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Uimonen, Katri; Merikallio, Heta; Pääkkö, Paavo; Harju, Terttu; Mannermaa, Arto; Palvimo, Jorma; Kosma, Veli-Matti; Soini, YlermiGASC1 (gene amplified in squamous cell carcinoma 1) encodes a nuclear protein that epigenetically catalyses the lysine demethylation of histones. We investigated the expression of GASC1 in different histological subtypes of lung cancer (n=289). Percentage value of GASC1 immunohistochemical expression was evaluated separately in the nuclei and cytoplasms of epithelial cancer cells. The results were compared with clinicopathologic factors and the smoking history of the patients. In lung tumor cells, 38% of nuclei and 54% of the cytoplasms stained positive for GASC1. Adenocarcinomas expressed more GASC1 nuclear (p=0.00011) and cytoplasmic (p=0.00074) positivity than squamous cell carcinoma. Smokers displayed less nuclear and cytoplasmic GASC1 expression than non-smokers (p=0.028 and p=0.036, respectively). Similarly, patients with more cytoplasmic positive staining had fewer pack years (p=0.043). Nuclear GASC1 expression had an impairing effect on survival when all histological lung cancer types were analysed together (p=0.039) and separately in squamous cell lung carcinoma (p=0.016). The results reveal that GASC1 expression is higher in adenocarcinoma than squamous cell carcinoma. Smoking decreases GASC1 expression in tumor cells, indicating that tobacco smoke may influence the methylation of histone 3 lysine residues in lung cancer. Nonetheless, nuclear GASC1 predicts a poor prognosis, especially in squamous cell carcinoma.
- PublicationOpen AccessExpression of Drebrin, an actin binding protein, in basal cell carcinoma, trichoblastoma and trichoepithelioma(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Mizutani, Yoko; Iwamoto, Ikuko; Kanoh, Hiroyuki; Seishima, Mariko; Nagata, Koh-ichiDrebrin, an F-actin binding protein, is known to play important roles in cell migration, synaptogenesis and neural plasticity. Although drebrin was long thought to be specific for neuronal cells, its expression has recently been reported in non-neuronal cells. As for skin-derived cells, drebrin was shown to be enriched at adhering junctions (AJs) in cultured primary keratinocytes and also be highly expressed in basal cell carcinoma (BCC) cells. Since BCC and two types of benign neoplasm, trichoblastoma and trichoepithelioma, are considered to derive from the same origin, follicular germinative cells, it is sometimes difficult to morphologically distinguish BCC from trichoblastoma and trichoepithelioma. In this study, we performed immunohistochemical staining of drebrin in BCC, trichoblastoma and trichoepithelioma, to examine whether drebrin could serve as a biomarker for BCC diagnosis. In western blotting, drebrin was detected highly and moderately in the lysates from a squamous cell carcinoma cell line, DJM-1, and normal human epidermis, respectively. In immunofluorescence analyses, drebrin was colocalized with markers of AJs and tight junctions in DJM-1 cells and detected at cellcell junction areas of human normal epidermis tissue. We then examined the distribution patterns of drebrin in BCC, trichoblastoma and trichoepithelioma. In BCC tissues, intense and homogeneous drebrin expression was observed mainly at tumor cell-cell boundaries. In contrast, drebrin was stained only weakly and nonhomogeneously in trichoblastoma and trichoepthelioma tissue samples. For differential diagnosis of BCC, drebrin may be a novel and useful marker.
- PublicationOpen AccessImmunohistochemistry of connexin43 and zonula occludens-1 in the myocardium as markers of early ischemia in autopsy material(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Kawamoto, Osamu; Michiue, Tomomi; Ishikawa, Takaki; Maeda, HitoshiImmunohistochemistry of the terminal complement complex (C5b-9) and fibronectin (FN) is useful to detect myocardial ischemia preceding necrosis in the postmortem diagnosis of sudden cardiac death. The present immunohistochemical study examined connexin43 (Cx43) and zonula occludens-1 (ZO-1) as markers of early myocardial ischemia in addition to the above-mentioned markers, using forensic autopsy cases of acute deaths due to myocardial infarction (MI, n=15) and acute ischemic heart disease (AIHD) without apparent myocardial necrosis (n=8), compared with those of acute mechanical asphyxiation (As, n=24) and drowning (D, n=10) as controls. Immunopositivities of each marker in the myocardium were semi-quantitatively graded by scoring. ZO-1, C5b-9 and FN were detected in the myocardial cytoplasm, whereas Cx43 and nonphosphorylated (np) Cx43 showed varied localizations at the intercalated disc, in the cytoplasm and along the lateral cell border. ZO-1 and FN showed a tendency to be detected more intensely in MI and IHD than in As and D. C5b-9 showed specific staining at the site of ischemia in MI (n=10/15) and AIHD (n=6/8), while the distribution of npCx43 was different in most cases of MI (n=14/15) and AIHD (n=5/8), compared with As and D; npCx43 positivity score was higher in the cytoplasm than at the intercalated disc, indicating redistribution due to myocardial ischemia. Such findings were detected in a few cases of As (n=3/24). These findings suggest that the combination of npCx43 and C5b-9 immunohistochemistry is useful for detecting early lesions of myocardial ischemia in sudden cardiac death.
- PublicationOpen AccessChronic administration of thiamine pyrophosphate decreases age-related histological atrophic testicular changes and improves sexual behavior in male Wistar rats(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Hernández-Montiel, H. L.; Vásquez López, C. M.; González-Loyola, J. G.; Vega-Anaya, G. C.; Villagrán-Herrera, M. E.; Gallegos-Corona, M. A.; Saldaña, C.; Ramos Gómez, M.; García Horshman, P.; García Solís, P.; Solís-S, J. C.; Robles-Osorio, M. L.; Ávila-Morales, J.; Varela-Echavarría, A.; Paredes Guerrero, R.Aging is a multifactorial universal process and constitutes the most important risk factor for chronic-degenerative diseases. Although it is a natural process, pathological aging arises when these changes occur quickly and the body is not able to adapt. This is often associated with the generation of reactive oxygen species (ROS), inflammation, and a decrease in the endogenous antioxidant systems, constituting a physiopathological state commonly found in chronicdegenerative diseases. At the testicular level, aging is associated with tissue atrophy, decreased steroidogenesis and spermatogenesis, and sexual behavior disorders. This situation, in addition to the elevated generation of ROS in the testicular steroidogenesis, provides a critical cellular environment causing oxidative damage at diverse cellular levels. To assess the effects of a reduction in the levels of ROS, thiamine pyrophosphate (TPP) was chronically administered in senile Wistar rats. TPP causes an activation of intermediate metabolism routes, enhancing cellular respiration and decreasing the generation of ROS. Our results show an overall decrease of atrophic histological changes linked to aging, with higher levels of serum testosterone, sexual activity, and an increase in the levels of endogenous antioxidant enzymes in TPP-treated animals. These results suggest that TPP chronic administration decreases the progression of age-related atrophic changes by improving the intermediate metabolism, and by increasing the levels of antioxidant enzymes.
- PublicationOpen AccessMaspin expression, subcellular localization and clinicopathological correlation in endometrial hyperplasia and endometrial adenocarcinoma(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Blandamura, Stella; Alessandrini, Lara; Saccardi, Carlo; Giacomelli, Luciano; Fabris, Alberta; Borghero, Angela; Litta, PietroMaspin expression in endometrial hyperplasia and endometrial endometrioid adenocarcinomas was assessed and its correlation with p53 and Ki-67 expressions and clinical outcome, as well as its potential to distinguish typical from atypical endometrial hyperplasia, were assessed in this study. Histological sections from 114 cases of endometrial endometrioid adenocarcinoma, 75 cases of endometrial hyperplasia (typical and atypical), and 23 normal endometrial tissue samples were examined. The most representative hematoxylin-eosin slides were selected and 2-3 micron-thick sections were cut for immunohistochemical staining with maspin, p53, and Ki-67 antibodies. While there was no maspin expression in normal endometrial cells, it was present in 14.5% of the patients with endometrial hyperplasia without atypia. Staining for maspin was positive in atypical hyperplasia and endometrial adenocarcinoma in, respectively, 45% and 49.1% of the cases studied. No statistically significant correlations were found between maspin and Ki-67 antibodies or p53 expression. Our findings showed that maspin expression, which generally correlates with a less aggressive behavior, is significantly higher in atypical hyperplasia and in endometrial endometrioid adenocarcinoma. Maspin positivity in endometrial hyperplasia could be used to identify pseudo-atypical hyperplasia and could be considered a potentially useful prognostic parameter in those cases in which adenocarcinomas are well differentiated.
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