Extramammary Paget’s diseases in men from the Shanghai area: its association with PSA level increase *SHI, GUOHAI; YE, DING‐WEI; YAO, XUDONG; ZHANG, SHILING; DAI, BO; ZHANG, HAILIANG; SHEN, YIJUN; ZHU, YAO; ZHU, YIPING; XIAO, WENJUN; MA, CHUNGUANG
doi: 10.1111/j.1600-0463.2010.02657.xpmid: 20854472
Shi G, Ye D‐W, Yao X, Zhang S, Dai B, Zhang H, Shen Y, Zhu Y, Zhu Y, Xiao W, Ma C. Extramammary Paget’s diseases in men from the Shanghai area: its association with PSA level increase. APMIS 2010; 118: 777–81. The aim of this study was to determine the incidence of prostate cancer in patients with extramammary Paget’s disease (EMPD). All cases of EMPD diagnosed between 1992 and 2007 in Shanghai Cancer Hospital were collected and analyzed for the incidence of prostate cancer. The median follow‐up was 78 months. In total, 38 cases of invasive and 10 cases of in situ EMPD had been registered. A second malignancy was found in 28.9% (11/38) of patients with invasive EMPD and in 30% (3/10) of patients with in situ EMPD. Patients had an increased risk of developing a second cancer compared with the general population (standardized incidence ratio: 1.7; 95% confidence interval 1.2–2.4). Sixteen patients had serum prostate‐specific antigen (PSA) level above 4 ng/mL; five developed prostate cancer, three of them with PSA levels beyond 100 ng/mL. The incidence of prostate cancer is 10.4% in this patient group. Patients with EMPD were more likely to have prostate cancer than the general population. Although the prognosis of EMPD is fairly good, a thorough search for a second tumor is recommended.
Generation of self‐renewing immature dendritic cells from mouse spleen that can take up mycobacteria and present antigens to T cellsPAL, RUBINA; MARWAHA, SARANDEEP; PEPPONI, ILARIA; MANN, JAMIE F.S.; PAUL, MATTHEW J.; RELJIC, RAJKO
doi: 10.1111/j.1600-0463.2010.02650.xpmid: 20854466
Pal R, Marwaha S, Pepponi I, Mann JFS, Paul MJ, Reljic R. Generation of self‐renewing immature dendritic cells from mouse spleen that can take up mycobacteria and present antigens to T cells. APMIS 2010; 118: 729–38. Dendritic cells (DC) play a key role in driving the adaptive immune response to Mycobacterium tuberculosis (MTB), the causative pathogen of tuberculosis (TB). However, studying these important yet very sparse immune cells in the context of MTB pathogenesis is severely restricted by the lack of suitable cell lines and the complexity of culturing of DC progenitors, usually obtained from the bone marrow. However, significant advances have been made towards generating long‐term DC cultures from various lymphoid tissues. Here, we report the evidence for generating a long‐term, self‐renewing DC culture from the Balb/c mouse spleen. We demonstrate that these cells, termed IDC‐3, have a myeloid DC origin, i.e. they are CD11c+CD11b++CD8‐α−F4/80+/− and that they also display a phenotype MHC‐II+CD16/32++CD80+/−CD86+, indicating that they are immature DC. Following incubation with Mycobacterium bovis BCG (Bacillus Calmette Guerin), the IDC‐3 efficiently took up bacteria and acquired the morphology of mature DC. Importantly though, when IDC‐3 were pre‐stimulated with a mycobacterial antigen in vitro, they were able to induce proliferation of T lymphocytes from mice immunized with the same antigen. The T‐cell stimulatory potential of IDC‐3 was further enhanced when the cells were co‐stimulated with an anti‐CD40 mAb. We therefore suggest that the IDC‐3 culture system could be a useful tool for studying the interaction of DC with mycobacteria.
A simple and economical method for the manual construction of frozen tissue arraysTSAO, SHU‐CHUAN; WU, CHUN‐CHIEH; WEN, CHIEN‐HUI; HUANG, YA‐CHUN; CHAI, CHEE‐YIN
doi: 10.1111/j.1600-0463.2010.02652.xpmid: 20854467
Tsao S‐C, Wu C‐C, Wen C‐H, Huang Y‐C, Chai C‐Y. A simple and economical method for the manual construction of frozen tissue arrays. APMIS 2010; 118: 739–43. Tissue microarray has been developed to enable multiple cores of tissue in one or more new paraffin blocks. Currently, almost all tissue microarrays are made by coring cylindrical tissues from formalin‐fixed and paraffin‐embedded tissues. The disadvantages of formalin‐fixed and paraffin‐embedded tissues include the poor preservation of antigenicity of certain proteins and mRNA degradation induced by the fixation and embedding process. However, frozen tissue array construction presents technical difficulties, and tissue array devices are expensive, particularly for small‐ and medium‐sized laboratories. We describe a simple manual method for producing well‐aligned tissue arrays by a capsule freeze method that allows us to successfully perform hematoxylin–eosin and immunohistochemical stain. All 120 tissue samples were collected and constructed into blocks by this capsule freeze method. The capsules were not affected during the sectioning process, and the capsule material always disappeared during the aqueous steps of the stain processing. The frozen tissue arrays were smoothly sectioned without the use of a tape transfer system and immunohistochemical study was performed with satisfactory results. This alternative method can be applied in any laboratory, and is both simple and economical.
Immunohistochemical characteristics of diffuse sclerosing variant of papillary carcinoma: comparison with conventional papillary carcinomaKOO, JA SEUNG; SHIN, EUNAH; HONG, SOON WON
doi: 10.1111/j.1600-0463.2010.02653.xpmid: 20854468
Koo JS, Shin E, Hong SW. Immunohistochemical characteristics of diffuse sclerosing variant of papillary carcinoma: comparison with conventional papillary carcinoma. APMIS 2010; 118: 744–52. Diffuse sclerosing variant of papillary carcinoma (DSVPC) is a rare variant of papillary thyroid carcinoma (PTC). It shows different clinicopathologic features to the conventional PTC, but the immunohistochemical characteristics of DSVPC are yet to be more clearly defined. The purpose of this study was to investigate the immunohistochemical features of DSVPC, which are different from those of PTC. Tissue microarray was constructed from the paraffin‐embedded tissue of 49 DSVPC and 50 conventional PTC samples. Immunohistochemical stains for p63, p53, galectin‐3, cytokeratin 19, β‐catenin, Bcl‐2, EMA, E‐cadherin, CD15, and CD56 were performed on each tissue microarray. Immunohistochemical stain for p63 was negative in all conventional PTCs, but 14 (28.6%) cases of DSVPC showed p63 expression (p = 0.000). p53 was expressed in 38 (76.0%) cases of conventional PTC and 21 (42.9%) cases of DSVPC (p = 0.001). Galectin‐3 was expressed in all 50 cases of conventional PTC, but eight (16.3%) cases of DSVPC did not express galectin‐3 (p = 0.003). EMA was expressed more in DSVPC (40.8%) than in conventional PTC (20.0%, p = 0.024). In univariate analyses, Bcl‐2 positivity (p = 0.016) and EMA negativity (p = 0.036) in DSVPC were associated with shorter time interval to tumor recurrence, but there was no significance for the two in multivariate analyses. DSVPC, a rare variant of PTC, has different immunohistochemical features from the conventional PTC, showing higher expression rate of p63 and lower expression rate of p53. It also shows galectin‐3 negativity and EMA positivity.
Skin wound healing in diabetic β6 integrin‐deficient miceJACOBSEN, JASPER N.; STEFFENSEN, BJØRN; HÄKKINEN, LARI; KROGFELT, KAREN A.; LARJAVA, HANNU S.
doi: 10.1111/j.1600-0463.2010.02654.xpmid: 20854469
Jacobsen JN, Steffensen B, Häkkinen L, Krogfelt KA, Larjava HS. Skin wound healing in diabetic β6 integrin‐deficient mice. APMIS 2010; 118: 753–64. Integrin αvβ6 is a heterodimeric cell surface receptor, which is absent from the normal epithelium, but is expressed in wound‐edge keratinocytes during re‐epithelialization. However, the function of the αvβ6 integrin in wound repair remains unclear. Impaired wound healing in patients with diabetes constitutes a major clinical problem worldwide and has been associated with the accumulation of advanced glycated endproducts (AGEs) in the tissues. AGEs may account for aberrant interactions between integrin receptors and their extracellular matrix ligands such as fibronectin (FN). In this study, we compared healing of experimental excisional skin wounds in wild‐type (WT) and β6‐knockout (β6−/−) mice with streptozotocin‐induced diabetes. Results showed that diabetic β6−/− mice had a significant delay in early wound closure rate compared with diabetic WT mice, suggesting that αvβ6 integrin may serve as a protective role in re‐epithelialization of diabetic wounds. To mimic the glycosylated wound matrix, we generated a methylglyoxal (MG)‐glycated variant of FN. Keratinocytes utilized αvβ6 and β1 integrins for spreading on both non‐glycated and FN‐MG, but their spreading was reduced on FN‐MG. These findings indicated that glycation of FN and possibly other integrin ligands could hamper keratinocyte interactions with the provisional matrix proteins during re‐epithelialization of diabetic wounds.
A new cleavage site for elastase within the complement component 3CLAESSON, ROLF; KANASI, ELENI; JOHANSSON, ANDERS; KALFAS, SOTIRIOS
doi: 10.1111/j.1600-0463.2010.02655.xpmid: 20854470
Claesson R, Kanasi E, Johansson A, Kalfas S. A new cleavage site for elastase within the complement component 3. APMIS 2010; 118: 765–68. The lysosomal enzyme elastase was earlier shown to cleave the complement molecule C3. During some preliminary experiments on the interactions of certain pathogenic bacteria with the innate defence mechanisms, we observed C3 cleavage, in the presence of elastase, to fragments not previously described. To elucidate this proteolytic reaction, the present study was conducted. Degradation of C3 in mixtures with elastase or cathepsin G was detected by an immunoblot procedure using anti‐C3c and anti‐C3d antibodies after separating the proteins by SDS‐PAGE. Certain C3 fragments were analysed for amino acid sequence. The results revealed the existence of a cleavage site for elastase at the position alanine1350/lysine1351 of the C3 molecule, which has not been previously described. The fragment resulted from this cleavage has a size of about 39 kDa and it contains a part or the whole of C3d. This cleavage was distinct from the one previously described at position 987/988, which gives a 34 kDa C3d‐containing fragment.
Expression of ezrin, Bcl‐2, and Ki‐67 in chondrosarcomasSÖDERSTRÖM, MIRVA; PALOKANGAS, TUIRE; VAHLBERG, TERO; BÖHLING, TOM; ARO, HANNU; CARPEN, OLLI
doi: 10.1111/j.1600-0463.2010.02656.xpmid: 20854471
Söderström M, Palokangas T, Vahlberg T, Böhling T, Aro H, Carpen O. Expression of ezrin, Bcl‐2, and Ki‐67 in chondrosarcomas. APMIS 2010; 118: 769–76. The aim of the present study was to investigate whether the expression of ezrin, a membrane‐cytoskeleton linker and regulator of cellular signaling, is associated with clinical features of chondrosarcoma. For this purpose, we studied the expression of ezrin in 54 chondrosarcomas by immunohistochemistry and correlated the expression with other tumor characteristics, markers of proliferation, apoptosis and with clinical parameters. The intensity of ezrin staining increased with the histologic grade, and a significant positive association existed between the tumor grade and ezrin expression (p = 0.0475). In addition, there was a positive correlation between the expression of ezrin and Bcl‐2, an anti‐apoptotic protein (r = 0.83, p < 0.0001), as well as between ezrin expression and increased proliferation as measured by Ki‐67 index (r = 0.70, p < 0.0001). The positive correlation of ezrin expression with Bcl‐2 and Ki‐67 as well as with tumor grade suggests that an aggressive behavior of chondrosarcoma may be related to activation of ezrin and that ezrin inhibitors could provide a much needed adjuvant therapy in chondrosarcomas. In conclusion, our results indicate that high ezrin expression correlates with aggressive features of chondrosarcomas. Further analyses on the pathways downstream of ezrin are warranted.
Increased expression of epidermal fatty acid‐binding protein by alveolar macrophages during acute rejection of rat lungsHOLLER, JULIA; ZAKRZEWICZ, ANNA; GARN, HOLGER; HIRSCHBURGER, MARKUS; KUMMER, WOLFGANG; PADBERG, WINFRIED; GRAU, VERONIKA
doi: 10.1111/j.1600-0463.2010.02662.xpmid: 20854474
Holler J, Zakrzewicz A, Garn H, Hirschburger M, Kummer W, Padberg W, Grau V. Increased expression of epidermal fatty acid‐binding protein by alveolar macrophages during acute rejection of rat lungs. APMIS 2010; 118: 791–800. In the lung, epidermal fatty acid‐binding protein (E‐FABP) is expressed by alveolar macrophages (AM) and alveolar epithelial cells type II (AEII). E‐FABP may regulate macrophage activation and is involved in the metabolism of surfactant phospholipids. As macrophage activation and surfactant dysfunction are associated with rejection, we hypothesize that E‐FABP expression is changed during acute rejection of pulmonary grafts. Orthotopic left lung transplantations were performed in the Dark Agouti to Lewis and in the isogeneic Lewis to Lewis rat strain combinations. E‐FABP expression was analyzed in the lung by immunohistochemistry, immunoblotting and quantitative reverse transcription‐polymerase chain reaction (RT‐PCR). Alveolar leukocytes obtained by bronchoalveolar lavage were analyzed by RT‐PCR. Immunohistochemistry of isografts revealed strong E‐FABP immunoreactivity in AEII and a moderate immunoreactivity in AM. In allografts undergoing acute rejection, AM exhibiting increased E‐FABP immunoreactivity accumulated. Immunoblots revealed a single band at 15 kDa, which corresponds to the expected molecular mass of E‐FABP. The levels of E‐FABP mRNA were higher in allografts than in isografts and control lungs. Furthermore, alveolar leukocytes isolated by bronchoalveolar lavage from allografts displayed higher E‐FABP mRNA expression levels than leukocytes from isografts and controls. In conclusion, we demonstrate for the first time upregulation of E‐FABP expression in AM during severe inflammation.