Histology and histopathology Vol.29, nº 4 (2014)
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- PublicationOpen AccessPrognostic impact of NDRG2 and NDRG3 in prostate cancer patients undergoing radical prostatectomy(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) Ren, Guo-feng; Tang, Ling; Yang, Ai-qing; Jiang, Wei-wei; Huang, Yi-mingAim: To investigate the clinicopathologic significance of NDRG2 and NDRG3, and their involvement in recurrence-free survival (RFS) and overall survival (OS) of prostate cancer (PCa). Methods: NDRG2 and NDRG3 expression in 206 pairs of primary PCa and corresponding noncancerous prostate tissue samples from the same specimens were detected by immunohistochemistry. The association of NDRG2 and NDRG3 expression with the clinicopathologic features and with the prognosis of PCa was subsequently assessed. Results: In PCa tissues, NDRG2 expression was significantly downregulated, while NDRG3 expression was significantly upregulated (both P<0.001), compared with those in corresponding noncancerous prostate tissues. In addition, the downregulation of NDRG2 in PCa tissues was significantly correlated with advanced pathological stage (P=0.001), positive metastatic status (P=0.001) and high Gleason score (P=0.003), while the upregulation of NDRG3 in PCa tissues was significantly correlated with advanced pathological stage (P=0.006), positive metastatic status (P=0.001) and lymph node status (P=0.002). Furthermore, multivariate survival analysis showed low NDRG2 and high NDRG3 immunoreactivities were both significantly associated with short RFS and short OS in PCa independently of routine clinicopathological predictors. Conclusion: Our data offer convincing evidence for the first time that the aberrant expression of NDRG2 and NDRG3 may contribute to the malignant progression of PCa. More importantly, both the downregulation of NDRG2 and the upregulation of NDRG3 may be efficient prognostic indicators for PCa. Histol Histopathol 29, 535-542 (2014)
- PublicationOpen AccessEpithelial expression of vanilloid and cannabinoid receptors: a potential role in burning mouth syndrome pathogenesis(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) Borsani, Elisa; Majorana, Alessandra; Cocchi, Marco Angelo; Conti, Giulio; Bonadeo, Sara; Padovani, Alessandro; Lauria, Giuseppe; Bardellini, Elena; Rezzani, Rita; Rodella, Luigi FabrizioBurning mouth syndrome (BMS) is an intra-oral burning sensation for which presently no medical or dental causes have been found, and in which the oral mucosa appears normal. It remains an unknown disease for which there is still no long-term treatment. The aim of this study was to assess the epithelial alteration of transient receptor potential vanilloid channel type 1 (TRPV1) and cannabinoid receptors type 1 (CB1) and type 2 (CB2) in the human tongue. The study was performed on eight healthy controls and eight BMS patients. All patients underwent a 3-mm punch biopsy at the anterolateral aspect of the tongue close to the tip. TRPV1, CB1 and CB2 immunohistochemistry was carried out showing an altered expression of all receptors. In BMS patients there was increased TRPV1, decreased CB1 and increased CB2 expression in tongue epithelial cells also associated with a change in their distribution. It would appear that these receptors are related to BMS. These data could be useful for future characterization of BMS epithelial markers and therapy. Histol Histopathol 29, 523-533 (2014)
- PublicationOpen AccessEGFR, KRAS, BRAF, and PIK3CA characterization in squamous cell anal cancer(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) Martin, Vittoria; Zanellato, Elena; Franzetti-Pellanda, Alessandra; Molinari, Francesca; Movilia, Alessandra; Paganotti, Alessia; Deantonio, Letizia; De Dosso, Sara; Assi, Agnese; Crippa, Stefano; Boldorini, Renzo; Mazzucchelli, Luca; Saletti, Piercarlo; Frattini, MiloBackground: Combined chemoradiation therapy is the gold standard in the treatment of squamous cell anal cancer (SCAC). However, even if the response rate is very high, many patients eventually relapse or experience a recurrence, thus requiring an invasive surgical procedure that has severe side effects. Most SCAC tumors overexpress epidermal growth factor receptor (EGFR); therefore, it is reasonable to consider anti-EGFR drugs as a new treatment option, as demonstrated by anecdotal reports. Promising results obtained in other solid tumors, both squamous and non-squamous, have revealed that an increase in the EGFR gene copy number may predict the efficacy of anti-EGFR therapies, while the presence of mutations in downstream members of the EGFR pathway may confer resistance. These markers have been only sporadically considered in SCAC. Methods: We investigated the status of the EGFR gene using FISH and examined KRAS, BRAF, and PIK3CA hot-spots mutations using sequencing analysis in a cohort of 84 patients affected by SCAC. Results: Twenty-eight patients (34%) showed an increase in EGFR gene copy number due to amplification (4%) or to polysomy (30%). KRAS and PIK3CA gene mutations were found in 4 (5%) and 13 patients (16%), respectively. No mutations were found in the BRAF gene. Conclusions: The characterization of the EGFR pathway may help in identifying different subgroups of SCAC that have specific molecular features, which may have implications in what targeted therapies are used to treat each patient. Histol Histopathol 29, 513-521 (2014)
- PublicationOpen AccessToxicological aspects of injectable gold-hyaluronan combination as a treatment for neuroinflammation(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) Pedersen, Dan Sonne; Locht, Linda J.; Tran, Thao P.; Markholt, Sara; Rungby, Jørgen; Larsen, AgneteSecondary inflammatory reactions to stroke or trauma contribute to irreplaceable loss of brain tissue of the affected patients. Likewise, neuroinflammatory processes are the main pathophysiological feature in Multiple Sclerosis (MS), a common neurodegenerative disease among young adults. In the search for safe and efficient ways to reduce inflammation within nervous tissue older immunosuppressive remedies have been re-investigated. The anti-inflammatory properties of gold salts are well known but result in uncontrollable systemic spread of gold ions, generating side effects such as nephrotoxicity, limiting their use. Recent studies have circumvented this obstacle by introducing metallic gold implants as a localized source of immune-modulating gold ions and suspension in hyaluronic acid (HA) enables injection of small amounts of gold in the natural spaces of the brain. By injecting >25 µm gold beads in HA intracerebrally we recently showed a slowing of disease progression in a rodent model of MS. The toxicological aspects were, however, not assessed. The present study investigates the viability of neuronal and macrophage cell cultures exposed to the gold/HA combination and the possible risk associated with unilateral gold/HA injection in young Balb/CA mice in the first 7 to 21 days of gold-exposure. Tracing by autometallography of gold accumulations throughout the brain exhibited sparse gold uptake in glia and neurons of hippocampus and cortex, and striatum and cerebellum were void of staining. No systemic spread of gold was seen in liver or kidney, nor were there signs of obstruction of the ventricular system. Both cell cultures of J774 macrophages and CCL neurons accumulated gold from gold/HA-exposure with no signs of reduced viability. In conclusion, our findings indicate that gold/HA is not overtly neuro- or cytotoxic, nor does intraventricular exposure result in widespread gold accumulation or tissue damage, warranting further studies into the pharmacological properties of this novel form of gold treatment. Histol Histopathol 29, 447-456 (2014)
- PublicationOpen AccessExpression of 11ß-hydroxysteroid dehydrogenase type 2 is deregulated in colon carcinoma(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) Moravec, Martin; Švec, Jiří; Ergang, Peter; Mandys, Václav; Řeháková, Lenka; Zádorová, Zdena; Hajer, Jan; Kment, Milan; Pácha, JiříAlthough the effects of glucocorticoids on proliferation, differentiation and apoptosis are well known, and steroid hormones have been identified to play a role in pathogenesis and the development of various cancers, limited data are available regarding the relationship between the local metabolism of glucocorticoids and colorectal adenocarcinoma (CRC) formation. Glucocorticoid metabolism is determined by 11ß-hydroxysteroid dehydrogenases type 1 and 2 (11HSD1, 11HSD2), which increase the local concentration of cortisol due to the reduction of cortisone, or decrease this concentration due to the oxidation of cortisol. The objective of this study was to evaluate the extent of 11HSD1 and 11HSD2 mRNA in pre-malignant colorectal polyps and in CRC. The specimens were retrieved from patients by endoscopic or surgical resection and the expression of 11HSD1 and 11HSD2 was measured by real-time PCR. The polyps were of the following histological types: hyperplastic polyps and adenomas with low- or high-grade dysplasia. The neoplastic tissue of CRC obtained during tumor surgery was also studied. It was found that 11HSD2 was not only downregulated in CRC but already in the early stages of neoplastic transformation (adenoma with low-grade dysplasia). In contrast, the level of 11HSD1 was significantly increased in CRC but not in pre-malignant polyps. The results demonstrate that the downregulation of 11HSD2 gene expression is a typical feature of the development of colorectal polypous lesions and their transformation into CRC. Histol Histopathol 29, 489-496 (2014)
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