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 AccessM1- and M2-macrophage polarization in thioacetamide (TAA)-induced rat liver lesions; a possible analysis for hepato-pathology(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) Wijesundera, Kavindra Kumara; Izawa, Takeshi; Murakami, Hiroshi; Tennakoon, Anusha Hemamali; Golbar, Hossain M.; Katou-Ichikawa, Chisa; Tanaka, Miyuu; Kuwamura, Mitsuru; Yamate, Jyoji“Classically activated macrophages (M1)” and “alternatively activated macrophages (M2)”, which appear in injured tissues, control either inflammation or remodeling. The mechanism remains unclear. To clarify the M1-/M2-macrophage polarization in acute liver injury, M1- and M2-related factors were analysed in F344 rats by a single injection of TAA (300 mg/kg BW), and liver samples were collected on post injection (PI) hour 10 and days 1 to 10. Macrophage immunopheno-types were analyzed by single and double immuno-labeling. M1-/M2-related factors were analyzed by real-time RT-PCR. On PI hour 10 (when centrilobular lesions were not still developed), expressions of IFN-γ, TNF-α, IL-1ß, and IL-6 for M1, and IL-4 for M2 were already increased, followed by increased expressions of IL-10 and TGF-ß1 for M2 on PI days 1-3 with development of centrilobular lesions and subsequent reparative fibrosis. On PI hour 10, CD204+ and MHC class II+ macrophages already increased in the intact periportal/Glisson’s sheath regions, accompanied by an increased number of granzyme B+ NK cells. Reactive cells at PI hour 10 might produce M1-related factors. In addition to these macrophages, CD68+ and CD163+ macrophages, and CD3+ T cells appeared in the injured centrilobular region on PI days 1-3; there were macrophages reacting simultaneously to CD68/MHC class II, CD163/MHC class II, CD68/CD204, CD163/CD204, and MHC class II/CD204 in varying degrees. Although CD68+ and CD163+ macrophages are regarded as M1- and M2-types, respectively, the double labeling indicated that macrophage immunophenotypes are interchangeable in injured regions and subsequent fibrosis. An M1-/M2-macrophage paradigm would be useful to analyze hepatotoxicity and to understand the pathogenesis. Histol Histopathol 29, 497-511 (2014)
- PublicationOpen AccessGender-related differences in kidney of rats with chronic renal failure(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) Lemos, Carla C.S.; Mandarim-de-Lacerda, Carlos A.; Carvalho, Jorge J.; Bregman, RachelChronic renal failure is characterized by adaptive mechanisms secondary to the loss of functioning nephrons. Clinical and experimental studies suggest participation of gender-related hormones on renal function and progression of chronic renal failure. We evaluated the effect of castration on renal alterations in male and female Wistar control rats and after 30 days of chronic renal failure (CRF) induced by 5/6 nephrectomy. The CRF male group showed higher proteinuria. Glomerular hypertrophy was similar amogroups. Podocyte morphology showed disorders of foot processes and thickening of the basement membrane in the CRF male group. The CRF female group showed fewer alterations compared to males. Castration changed the profile in CRF male animals and the filtration barrier was preserved. CRF males showed the presence of alfa-smooth muscle actin suggesting an early prefibrotic event in this group. After castration this phenomenon was not observed. Noteworthy, in females, castration exacerbated the presence of alfa-smooth muscle actin. In summary, proteinuria was higher in males and appeared early in the course of CRF, probably contributing to fibrotic events. Data were influenced by gender suggesting that male sex hormones aggravate renal alterations. Histol Histopathol 29, 479-487 (2014)
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