Histology and histopathology Vol.33, nº3 (2018)
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- PublicationOpen AccessEcology of melanoma cell(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Lacina, Lukáš; Kodet, Ondřej; Dvořánková, Barbora; Szabo, Pavol; Smetana Jr, KarelMelanoma represents a cancer with increasing incidence worldwide and limited curability of advanced stages of the disease. Similarly to other types of tumors, the microenvironment is an important factor that participates in the control of melanoma biological properties. This review summarizes data regarding the role of the microenvironment, namely fibroblasts, keratinocytes and infiltrating immune cells, on melanoma growth and spreading. The role of embryonic microenvironment on melanoma cell biological properties is also discussed. The potential of therapeutic targeting of the melanoma microenvironment is demonstrated.
- PublicationOpen AccessHigh-grade renal cell carcinoma with emperipolesis: Clinicopathological, immunohistochemical and molecular-genetic analysis of 14 cases(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Rotterova, Pavla; Martinek, Petr; Alaghehbandan, Reza; Prochazkova, Kristyna; Damjanov, Iván; Rogala, Joanna; Suster, Saul; Perez Montiel, Delia; Alvarado Cabrero, Isabel; Sperga, Maris; Švajdler, Marián; Michalova, Kvetoslava; Pivovarcikova, Kristyna; Daum, Ondrej; Hora, Milan; Dusek, Martin; Ondic, Ondrej; Stehlikova, Adela; Michal, Michal; Hes, OndrejEmperipolesis has recently been described as a constant feature of “biphasic squamoid” papillary renal cell carcinoma (BPRCC). We also noticed this in some high-grade (HG) RCC, which promoted the present study to estimate the incidence of emperipolesis in RCCs and to describe them in further detail. 14 cases of HGRCC showing emperipolesis were retrieved from our registry. Microscopic examination of filed slides was supplemented with immunohistochemical and molecular-genetic analyses using paraffin embedded tissue. 12 of 14 patients were males with a mean age of 58.6 years (range 41-72 years). Tumor size ranged from 6-16.5 cm (mean of 8.8 cm). Follow up data were available for 8/14 patients (range 0.5-10 years). Metastases were documented in 6 cases. All tumors showed solid-alveolar growth patterns with focal pseudopapillary features, and were composed of large cells with bizarre nuclei and eosinophilic rhabdoid-like cytoplasm. Emperipolesis was a constant and prominent feature in large bizarre cells. All cases were positive for OSCAR, CANH 9, vimentin, cyclin D1, INI-1, and myoD1, while negative for melanocytic markers, CK 7, myoglobin, cathepsin K, and TFE3. VHL gene abnormalities were found in 6/9 analyzable cases, of which 2 demonstrated polysomy of chromosomes 7, 17. Emperipolesis is a rare histomorphologic feature which can be seen not only in BPRCCs but also in highgrade CCRCCs. All RCC cases with prominent emperipolesis fulfilled both morphologic and immunohistochemical diagnostic criteria of high-grade CCRCC. The majority of patients with available follow up information developed metastases.
- PublicationOpen AccessThe tick-derived rBmTI-A protease inhibitor attenuates the histological and functional changes induced by cigarette smoke exposure(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Lourenço, Juliana D.; Ito, Juliana T.; Cervilha, Daniela A.B.; Sales, Davi S.; Riani, Alyne; Suehiro, Camila L.; Genaro, Isabella S.; Duran, Adriana; Puzer, Luciano; Martins, Milton A.; Sasaki, Sérgio D.; Lopes, Fernanda D.T.Q.S.Introduction. Smoking is the main risk factor for chronic obstructive pulmonary disease development and cigarette smoke (CS) exposure is considered an important approach to reproduce in rodents this human disease. We have previously shown that in an elastase-induced model of emphysema, the administration of a protease inhibitor (rBmTI-A) prevented and attenuated tissue destruction in mice. Thus, in this study we aimed to verify the effects of rBmTI-A administration on the physiopathological mechanisms of CS-induced emphysema. Methods. Mice (C57BL/6) were exposed to CS or room air for 12 weeks. In this period, 3 nasal instillations of rBmTI-A inhibitor or its vehicle were performed. After euthanasia, respiratory mechanics were evaluated and lungs removed for analysis of mean linear intercept, volume proportion of collagen and elastic fibers, density of polymorphonuclear cells, macrophages, and density of positive cells for MMP-12, MMP-9, TIMP-1 and gp91phox. Results. The rBmTI-A administration improved tissue elastance, decreased alveolar enlargement and collagen fibers accumulation to control levels and attenuated elastic fibers accumulation in animals exposed to CS. There was an increase of MMP12, MMP-9 and macrophages in CS groups and the rBmTIA only decreased the number of MMP-12 positive cells. Also, we demonstrated an increase in gp91phox in CS treated group and in TIMP-1 levels in both rBmTI-A treated groups. Conclusion. In summary, the rBmTI-A administration attenuated emphysema development by an increase of gp91phox and TIMP-1, accompanied by a decrease in MMP-12 levels.
- PublicationOpen AccessExpression of TIM-3 and LAG-3 in extranodal NK/T cell lymphoma, nasal type(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Feng, Yuhua; Zhong, Meizuo; Liu, Yiping; Wang, Leyuan; Tang, YouhongObjective. To investigate the expression of TIM-3 and LAG-3 in extranodal NK/T cell lymphoma, nasal type (ENKTL), and evaluate the clinical and prognostic significance of TIM-3 and LAG-3 in ENKTL. Methods. A total of 61 human paraffin-embedded specimens including 41 ENKTL and 20 rhinitis were involved. We performed immunohistochemistry to detect the expression of TIM-3 and LAG-3. We analyzed correlation between expression of TIM-3 and LAG-3 and clinicopathological features of ENKTL. Results. TIM-3 was positively expressed in 95 (39/41) ENKTL compared with 55% (11/20) in rhinitis, LAG-3 was positively expressed in 95 (39/41) ENKTL compared with 45% (9/20) in rhinitis. A positive correlation was found between TIM-3 and LAG-3. TIM3 and LAG-3 had no significant correlation with ENKTL patients’ age, gender, international prognostic index (IPI) score, B symptoms, LDH level, Ann Arbor stage and treatment regimens. High expression of TIM-3, high IPI score, elevated LDH level and late Ann Arbor stage were shown to be correlated with worse progression free survival (PFS). A multivariate COX regression model show that TIM-3 high expression rate was an independent prognostic factor for ENKTL patients’ PFS. Conclusions. Our findings indicate that TIM-3 might be a promising predictive indicator for the ENKTL patients.
- PublicationOpen AccessInterleukin 6 receptor (IL-6R) was an independent prognostic factor in cervical cancer(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Luan, Shaohong; An, Zhijie; Bi, Shuna; Chen, Long; Fan, JunIL-6 has been found to be associated with poor response to chemoradiotherapy and poor overall prognosis of patients with cervical cancer. However, little is known about the clinicopathological significance of IL-6 receptor (IL-6R) expression in the setting of cervical cancer. To investigate the clinicopathological meaning of IL-6R in cervical cancer, expression of IL6R was detected using immunohistochemistry in cervical cancer tissue microarray composed of 98 cases of cervical cancer and paired normal controls. As further confirmation of expression trend, western-blotting was conducted in another independent 36 pairs of cervical cancer and matched normal controls. Subsequently, the statistical correlation between IL-6R expression and clinicopathological variables was analyzed, including demographic, TNM stage, clinical grading and overall prognosis. IL-6R expression was shown to be remarkably associated with lymph node metastasis, recurrence and overall prognosis. Moreover, only IL-6R expression was observed to be an independent prognostic factor among these variables that could potentially influence the overall prognosis of patients with cervical cancer. In conclusion, IL-6R was shown to be an independent prognostic factor for patients with cervical cancer.
- PublicationOpen AccessThe role of RhoC in malignant tumor invasion, metastasis and targeted therapy(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Guan, Xue; Chen, Shuo; Zhao, YangAs an important member of the RhoGTPase family, RhoC has various biological functions, such as regulating cytoskeleton reorganization, influencing cell adhesion, and migration. During recent decades, RhoC has been proven to be involved in the invasion and metastasis of malignant tumor and is thus a promising target of tumor therapy. This review focuses on the molecular mechanism of RhoC in invasion and metastasis of malignant tumors, as well as its research prospects as a potential target for tumor therapy.
- PublicationOpen AccessExpression of CD34 and CD146 vascular markers contributes to the immunological function of the human palatine tonsil(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Jovic, Marko; Avramović, Verica; Vlahović, Predrag; Velickov, Aleksandra; Petrović, VladimirThe fundamental function of the palatine tonsil is the immune response to airborne and foodborne pathogenic agents. Small blood vessels have an important role in the provision of a special microenvironment in which the immune response occurs. In this study, we investigated the expression of vascular markers CD34 and CD146 and basal lamina marker - type IV collagen - in the small blood vessels of the human palatine tonsil in the context of their role in the immunological function of the tonsil. The tonsils were collected after tonsillectomy from ten patients with chronic tonsillitis, aged 18-28 years. Five-µm-thick paraffin sections were routinely stained with haematoxylin and eosin, while the studied markers (CD34, CD146 and type IV collagen) were detected immunohistochemically using LSAB2/HRP method. CD34 was expressed equally in the capillaries within and below the crypt epithelium, in lymphoid follicles and in high endothelial venules localized para- and interfollicularly. CD146 molecule was expressed on the luminal surface of endothelial cells in the capillaries of the crypt epithelium, while its expression in high endothelial venules was seen on the luminal and lateral surfaces of the cuboidal endothelial cells. In contrast to the basal lamina of intraepithelial capillaries, where collagen IV-immunopositivity is mostly seen as a continuing line, the basal lamina of high endothelial venules was seen as a two- or three-layered structure beneath the cuboidal endothelial cells. The specifics of expression of CD34, CD146, and type IV collagen confirm the morphofunctional specialization of endothelium in crypt epithelium capillaries, and also in endothelium of high endothelial venules, which is directly associated with the role of these vessels in the immune function of the tonsil.
- PublicationOpen AccessRole of Ca2+ and ion channels in the regulation of apoptosis under hypoxia(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Wang, Miaohong; Tan, Jin; Miao, Yuyang; Li, Mengmeng; Zhang, QiangHypoxia is a kind of common pathological condition existing in various diseases such as sleep apnea syndrome, myocardial infarction and stroke, which can precipitate the onset of diseases through inducing cell apoptosis. Ca2+ is the ubiquitous message in cell. Given the crucial role of Ca2+ in physiology, intracellular Ca2+ overload is a significant regulator of apoptosis. Numerous experiments show that hypoxia may cause changes of multiple cellular Ca2+ channels, for instance, Na+/Ca2+ Exchanger (NCX), L-type voltage dependent Ca2+ channel (L-VDCC), inositol triphosphate receptors (IP3R) and so on, which contribute to intracellular Ca2+ overload, thus eventually triggering cell apoptosis. However, the mechanisms underlying different Ca2+ channels involved in hypoxic apoptosis are complex. For example, chronic hypoxia or acute hypoxia may select different Ca2+ channels to influence cell apoptosis. In addition, intracellular Ca2+ overload may initiate different apoptotic pathways due to hypoxic duration. Furthermore, different locations in the cell of specific Ca2+ channels activated by hypoxia will determine different apoptosis signaling pathways. Moreover, activation of different Ca2+ channel isoforms will result in different outcomes of the cell under hypoxia. Hence, we aim to highlight the potential mechanisms of the main Ca2+ channels in regulation of apoptosis under hypoxic stress.
- PublicationOpen AccessHistopathological changes associated to an absorbable fibrin patch (Tachosil®) covering in an experimental model of high-risk colonic anastomoses(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) García Vásquez, C.; Gómez García de las Heras, S.; Pastor Idoate, C.; De Pablo, D.; Fernández Aceñero, M.J.Background. TachoSil® is a fibrin sponge that contains fibrinogen and thrombin and is a useful adjuvant to enhance control of air leaks in thoracic surgery and to control bleeding in vascular and general surgery. Its use in intestinal surgery to prevent suture dehiscence is currently under investigation. Material and Methods. We report the results of a prospective randomized experimental study on 33 large white pigs in which a high-risk suture was created by induction of ischemia. We randomly employed TachoSil® to cover the anastomosis in half of the animals compared to a control group of uncovered anastomosis. After euthanasia, postmortem analysis was performed describing the findings related to anastomotic leakage, peritonitis and grade of adhesions. The entire anastomosis was resected in bloc and sent for histopathological analysis. A single blinded-pathologist evaluated the histopathological features of the specimens. Results. We found statistically significant differences favouring the patch in decreasing leakage in the covered group. The healing process did not show significant differences between groups, although a higher rate of microscopic abscess was observed in the covered group. Conclusion. The use of fibrin sealants covering highrisk intestinal sutures has a positive effect in avoiding macroscopic anastomotic leakage. The patch did not have any influence in the anastomotic healing process, however, as a result of the effect in containing the inflammatory response, it may increase the rate of abscess.
- PublicationOpen AccessRelationship between non-TRU lung adenocarcinomas and bronchiolar metaplasia - potential implication in their histogenesis -(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Okudela, Koji; Kojima, Yoko; Matsumura, Mai; Arai, Hiromasa; Umeda, Shigeaki; Tateishi, Yoko; Mitsui, Hideaki; Suzuki, Takehisa; Tajiri, Michihiko; Ogura, Takashi; Ohashi, KenichiLung adenocarcinomas (ADCs) have been roughly divided into two groups: the terminal respiratory unit (TRU) type and non-TRU type. These ADCs appear to develop through exclusive carcinogenetic pathways because of differences in their cellular morphologies and the profiles of protein expression and genetic alterations. The TRU type develops from atypical adenomatous hyperplasia as a precursor. On the other hand, the histogenesis of the non-TRU type has not yet been defined in detail. We herein investigated histopathological changes in the non-tumor lung tissues of patients with non-TRU-type ADCs in order to define their potential histogenesis. The non-TRU type preferentially occurs in patients with interstitial pneumonia, in whom tumors are located in honeycomb lesions and are associated with bronchiolar metaplasia (BM). Among patients without interstitial pneumonia, non-tumor lung tissues from non-TRU-type ADCs were often affected by multiple BM. In these cases, tumors often were associated with BM. Metaplastic cells adjacent to non-TRU-type ADCs ectopically expressed HNF-4α, a marker for non-TRU-type ADCs. These results suggest that the non-TRU type develops through distinct histogenesis, in which BM is implicated.