1.Immunoreactivity of CD99 in Non-Hodgkin's Lymphoma: Unexpected Frequent Expression in ALK-positive Anaplastic Large Cell Lymphoma.
Chang Ohk SUNG ; Young H KO ; Sanghui PARK ; Kihyun KIM ; Wonseog KIM
Journal of Korean Medical Science 2005;20(6):952-956
To verify the spectrum of CD99-expressing lymphoid malignancy, an immunohistochemical study for CD99 was carried out in 182 cases of non-Hodgkin's lymphoma, including 21 lymphoblastic lymphomas, 11 small lymphocytic lymphomas, 9 mantle cell lymphomas, 12 follicular lymphomas, 37 diffuse large B cell lymphomas, 18 Burkitt's lymphomas, 28 NK/T-cell lymphomas, 8 angioimmunoblastic T-cell lymphomas, 23 peripheral T-cell lymphomas, unspecified, and 15 systemic anaplastic large cell lymphomas. CD99 was positive in all T-lymphoblastic lymphomas and in 60% of B-lymphoblastic lymphomas. Majority of T and NK cell lymphomas were negative for CD99, except anaplastic large cell lymphomas (ALCLs). Eight of 15 cases (54%) of ALCLs reacted with anti CD99 antibody. Seven of 10 (70%) ALK positive ALCLs expressed CD99, whereas only 1 of 5 (20%) ALK negative ALCLs were positive. Of the mature B-cell lymphomas, 5.4% (2/37) of diffuse large B cell lymphomas and 11.1% (2/18) of Burkitt's lymphomas expressed CD99. In conclusion, CD99 is infrequently expressed in mature B and T cell lymphomas, except ALK-positive ALCL. High expression of CD99 in ALK-positive ALCL is unexpected finding and its biologic and clinical significances have yet to be clarified.
Antigens, CD/*metabolism
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Blotting, Western
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Cell Adhesion Molecules/*metabolism
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Humans
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Immunohistochemistry
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Lymphoma, Large-Cell/enzymology/*immunology/pathology
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Lymphoma, Non-Hodgkin/enzymology/*immunology/pathology
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Protein-Tyrosine Kinase/immunology/*metabolism
2.A Case of Primary Gastric CD30-Positive Anaplastic Large-Cell Lymphoma.
Hun Ho SONG ; Gwang Ho BAIK ; Jung Hye KWON ; Keun Seok LEE ; Young Hee CHOI ; Kyung Chan CHOI ; Young Eui PARK
Journal of Korean Medical Science 2005;20(6):1062-1065
Gastric CD30-positive anaplastic large-cell lymphoma is a very rare disease. It is sometimes difficult to distinguish it from undifferentiated carcinoma, sarcoma and so on. We report here on a case of primary gastric anaplastic large-cell lymphoma. A 50-yr-old woman complained of epigastric pain and severe chest pain for 1 week. The gastroendoscopic examination revealed geographic mucosal irregularities with shallow ulceration at the antrum. She underwent a total gastrectomy. The gross finding of the resected stomach was an 8 x 4.5 cm sized ulceroinfiltrative lesion at the pyloric antrum along the lesser curvature. The microscopic examination revealed diffuse and solid proliferations of large atypical cells with pleomorphic nuclei. Immunohistochemically, the tumor cells were positive for CD30, vimentin and CD3, and this was a finding compatible with anaplastic large-cell lymphoma. To the best of our knowledge, this is the first such reported case in Korea.
Antigens, CD30/*metabolism
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Female
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Humans
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Immunohistochemistry
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Korea
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Lymphoma, Large-Cell/enzymology/*immunology/*pathology
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Middle Aged
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Protein-Tyrosine Kinase/metabolism
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Stomach Neoplasms/enzymology/*immunology/*pathology
3.Research progress on prognostic markers of chronic lymphocytic leukemia.
Jie MAO ; Zheng-rong MAO ; Ren ZHOU
Journal of Zhejiang University. Medical sciences 2010;39(3):250-256
Chronic lymphocytic leukemia (CLL) remains the most common adult leukemia. The recent progress on research of molecular and cellular genetics of CLL promotes the development of the diagnosis, treatment and prognosis for CLL patients. IGVH gene mutation status is the most important prognostic marker for CLL patients. Zeta-chain-associated protein kinase (ZAP-70) can be used as a surrogate marker for IGVH mutation status. CD38 is a type II transmembrane glycoprotein promoting B cell activation and proliferation, which can improve the survival of CLL cells and enhance their proliferation, so it also can be used as an independent prognostic indicator for CLL. Chromosome aberrations are found in more than 80% of CLL cases. The most frequent abnormalities are losses of chromosomal material, with deletions in band 13q14 being the most common. The most common gains of chromosomal material are trisomies 12q. Human leukocyte antigen G (HLA-G) is a non-classical HLA-I gene. Increased expression of HLA-G leads to the malignant progression of CLL, significantly shortens survival, indicating HLA-G might serve as a prognostic marker in CLL. Toll-like receptors (TLA) are important component of natural immunity. The combination of TLR agonists and release chemotherapy, monoclonal antibodies and tumor vaccines would bring a breakthrough for the treatment of CLL.
ADP-ribosyl Cyclase 1
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metabolism
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Chromosome Aberrations
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HLA Antigens
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metabolism
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HLA-G Antigens
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Histocompatibility Antigens Class I
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metabolism
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Humans
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Immunoglobulin Heavy Chains
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genetics
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Immunoglobulin Variable Region
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genetics
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Leukemia, Lymphocytic, Chronic, B-Cell
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genetics
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immunology
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metabolism
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Mutation
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Prognosis
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Sequence Deletion
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Toll-Like Receptors
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metabolism
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ZAP-70 Protein-Tyrosine Kinase
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metabolism
4.Prognostic factors for chronic lymphocytic leukemia with typical and atypical immunophenotype.
Xin CAO ; Wei XU ; Yu-Jie WU ; Chun QIAO ; Qiong LIU ; Lei FAN ; Kou-Rong MIAO ; Jian-Yong LI
Chinese Journal of Hematology 2009;30(7):450-453
OBJECTIVETo analyze the prognostic factors for chronic lymphocytic leukemia (CLL) with typical and atypical immunophenotype. The parameters analyzed included sex, age, Binet stages, absolute lymphocyte count (ALC), immunoglobulin heavy-chain variable region (IgVH) gene mutation status, ZAP-70 protein, CD38 expression and cytogenetic aberrations.
METHODSAccording to the clinical guideline and scoring system for CLL in Britain, among 77 patients, 61 patients with score 5 called typical immunophenotype CLL, 16 with score 4 or 3 were atypical immunophenotype CLL. Multiparameter flow cytometry was employed for immunophenotypic analysis in 77 CLL patients for CD5, CD19, CD23, FMC7, sIg, CD20, CD79b expression and ZAP-70 protein and CD38. IgVH mutation status was detected by multiplex RT-PCR and sequencing of the purified PCR amplification products. Fluorescence in situ hybridization (FISH) and a panel of probes were used to detect cytogenetic aberrations.
RESULTSThere was no significant difference between the two groups in sex, age, ZAP-70 and IgVH mutation status (P=0.398, P=0.189, P=0.268 and P=0.131, respectively). The incidence of ALC> or =50 x 10(9)/L, Binet B + C, CD38> or =30% in atypical CLL patients (43.8%, 87.5% and 43.8%, respectively) were higher than that in typical group (16.4%, 36.1% and 16.4%, respectively) (P=0.026, P<0.01 and P=0.026, respectively). The proportion of typical patients (26.8%) with a 13q14 deletion as sole abnormality was higher than that of atypical patients (7.6%), and that with deletion of 11q22 or 17p13 was lower than that of atypical patients (12.2% vs 46.2%) (P=0.022).
CONCLUSIONThere were obvious differences between the typical immunophenotype CLL and atypical CLL in ALC, Binet stages, CD38 expression level and cytogenetic aberrations.
ADP-ribosyl Cyclase 1 ; metabolism ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Immunoglobulin Variable Region ; genetics ; Immunophenotyping ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; immunology ; metabolism ; Male ; Middle Aged ; Mutation ; Neoplasm Staging ; Prognosis ; ZAP-70 Protein-Tyrosine Kinase ; metabolism
5.Abnormality of serum immunoglobulin in peripheral blood of patients with chronic lymphocytic leukemia.
Yuan-Dong ZHU ; Wei XU ; Kou-Rong MIAO ; Xin CAO ; Lei FAN ; Qiong LIU ; Lin YAO ; Yu-Jie WU ; Min HONG ; Jian-Yong LI
Journal of Experimental Hematology 2009;17(5):1159-1162
In order to investigate the relation of serum immunoglobulin (Ig) level to age, sex, disease stages and prognosis in chronic lymphocytic leukemia (CLL) patients, the levels of serum IgG, IgA and IgM in 83 CLL patients were detected by immune rate turbidimetry. the expressions of CD38 and ZAP-70 in CLL cells were determined by multi-parameter flow cytometry (FCM). The results showed that among the 83 CLL patients, the IgG, IgA and IgM levels were reduced in 12 (14.5%), 26 (31.3%) and 34 cases (41.0%) respectively. The incidence of Ig reduction was higher in Binet C stage than that in Binet A and B (p=0.011). There was higher incidence of Ig reduction in high-risk group of Rai stage than that in low-risk group (p=0.011). The positive rate of CD38 or ZAP-70 was significantly higher in Ig reduction group than that in normal Ig level group (p=0.033 and p=0.038 respectively). The positive rate of CD38 and ZAP-70 was also higer in advanced disease, and among them the positive rate of ZAP-70 expression in Binet C stage was obviously higer than Binet A and B (p=0.047). Nonetheless, there was no significant relationship of Ig level with gender and age (p>0.05). It is concluded that the function of humoral immunity in CLL patient is closely related to the disease stages. The serum Ig detection seems important for evaluating immunologic state and prognosis of CLL patients.
ADP-ribosyl Cyclase 1
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metabolism
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Adult
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Aged
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Aged, 80 and over
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Female
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Humans
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Immunity, Humoral
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Immunoglobulin A
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blood
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Immunoglobulin G
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blood
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Immunoglobulin M
;
blood
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Immunoglobulins
;
blood
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Leukemia, Lymphocytic, Chronic, B-Cell
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blood
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immunology
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Male
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Middle Aged
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Prognosis
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ZAP-70 Protein-Tyrosine Kinase
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metabolism
6.Progress in the study of allergic disease drugs targeting on IgE/FcepsilonRI signaling pathway.
Zhong-cheng LIU ; Hai-lang SHI ; Yan-fen ZHANG ; Li-jun ZHAO
Acta Pharmaceutica Sinica 2011;46(10):1161-1166
Allergic diseases have become global social health problems. The binding of IgE with its high affinity receptor FcepsilonRI plays a key step in I-type allergy. Recently, more and more key molecules on the IgE/FcepsilonRI signaling transduction pathway were to be the drug candidates against allergic diseases, with in-depth study of FcepsilonRI signal pathway gradually. The main drugs include molecule antibodies, peptides, vaccines, fusion proteins, small molecules, and other drugs related to IgE/FcepsilonRI. The recent progress in the study of mechanisms of representative drugs targeting on IgE/FcepsilonRI signaling pathway was reviewed in this article.
Aminophenols
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pharmacology
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therapeutic use
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Animals
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Anti-Allergic Agents
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pharmacology
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therapeutic use
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Antibodies, Anti-Idiotypic
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pharmacology
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therapeutic use
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Antibodies, Monoclonal, Humanized
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pharmacology
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therapeutic use
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Humans
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Hypersensitivity
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drug therapy
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immunology
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Immunoglobulin E
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metabolism
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Intracellular Signaling Peptides and Proteins
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antagonists & inhibitors
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Molecular Targeted Therapy
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Omalizumab
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Protein-Tyrosine Kinases
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antagonists & inhibitors
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Pyrimidines
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pharmacology
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therapeutic use
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Receptors, IgE
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metabolism
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Signal Transduction
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Syk Kinase
7.Design and expression of an inhibitor for HIV-1 targeting dendritic cell.
Meng ZHAO ; Qing XU ; Jiyun YU ; Yunzhou YU
Chinese Journal of Biotechnology 2011;27(8):1191-1197
Human immunodeficiency virus (HIV) infects the host cells by the fusion of viral and cell membranes. Blocking the combining between HIV and the receptors can prevent HIV from entering the host cells. We designed an invasion-inhibitor for HIV-1 targeting dendritic cell (DC), including 2 important HIV-1 receptors CD4 and CCR5, and 2 molecules Flt3-L and Mip-3alpha. With the synthetic gene of the inhibitor, 2 eukaryotic expression vectors pABK-CKR5-CD4/Flt3L-Mip3alpha (pABK-HIV-MF) and pABK-CKR5-CD4 (pABK-HIV-MT) were constructed and transfected into HEK 293 cells for expression. Results from RT-PCR, immunofluorescent assay, ELISA and Western blot approved that the invasion-inhibitor for HIV-1 was successfully and exactly expressed in the eukaryotic cells. Current study formed a solid base for the further research on the function of inhibitors for HIV-1 and elimination targeting DC.
Artificial Gene Fusion
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CD4 Antigens
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biosynthesis
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genetics
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Chemokine CCL20
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biosynthesis
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genetics
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Dendritic Cells
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immunology
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metabolism
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Genetic Vectors
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genetics
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HEK293 Cells
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HIV Envelope Protein gp120
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genetics
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HIV-1
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physiology
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Humans
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Receptors, CCR5
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biosynthesis
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genetics
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Receptors, HIV
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antagonists & inhibitors
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Transfection
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fms-Like Tyrosine Kinase 3
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biosynthesis
;
genetics
8.Relationship between epithelial-immunologic cells transdifferentiation and pseudoepitheliomatous granuloma lesion.
Du-yin JIANG ; Xiao-bing FU ; Wei CHEN ; Tong-zhu SUN ; Zhi-yong SHENG
Chinese Journal of Surgery 2004;42(7):400-405
OBJECTIVEInappropriate treatment at early stage of wound could result in the formation of pseudoepitheliomatous granuloma (PEG). The correlation of abnormal transdifferentiation of epithelial cells to immunologic cells and the occurrence of PEG lesion was investigated.
METHODSMorphological change of epithelial tissue was observed with histopathology in 11 specimens of PEG lesions and 6 specimens of normal skins from PEG edge (PEG-N) from 11 patients with damaged skin. The expression characteristics and distribution of pan-cytokeratin (CKp), IV type collagen, laminin (LM), epithelial cadherin (E-Cad), beta-catenin (beta-Cat), focal adhesion kinase (FAK), stem cell factor (SCF) and its receptor-c-Kit, proliferating cell nuclear antigen(PCNA), and cluster of differentiation-14 (CD14), CD68 and mast cell tryptase (MCT) in PEG were detected with the immunohistochemical and the indirect immunofluorescent double-staining.
RESULTSIn comparison with PEG-N, epithelial tissue take on squamous metaplasia, and stroma was infiltrated with intensive microvessels and inflammatory cells in the PEG lesion. Poor epithelial basal layer constitution, basal polarization, and migration of basal cells to stroma could be observed. In the ultrastructure, the loose intercellular junction of basal cells and the increased nucleus/cytoplasm ratio and intercellular space could be observed, neonatal monocytoid cells and macrophages and mast cells as a exuviate-like manner brooded from cytoplasm of original epithelial cells and basement membrane. protein expression of CKp and E-Cad by basal cells was significantly decreased, and the IV type collagen and LM protein could not be found in basement membrane of identical locus. By contrast, the immunoreactivity of beta-Cat and FAK was apparently increased. In addition, CD14(+) monocytes, CD68(+) macrophages, MCT(+) mast cells and CD68(+)/MCT(+) cells with various size, and these cells of stronger immuno-staining of SCF, c-Kit and PCNA antigen could be found in epithelial tissue and stroma.
CONCLUSIONEpithelial cells in PEG related to wound are characteristized by transdifferentiation of epithelial cells to immunologic cells, wich may be associated with local infectious and inflammatory reaction, ultimately resulting in enhancement the ratio of beta-Cat/E-Cad signal and activation SCF-c-Kit signal pathway. The phenomena of transdifferentiation epithelial cells in the PEG lesion will help to recognize of the neoplatic immune and trauma repair mechanism.
Adolescent ; Adult ; Aged ; Antigens, CD ; analysis ; Antigens, Differentiation, Myelomonocytic ; analysis ; Burns ; physiopathology ; Cadherins ; analysis ; Cell Differentiation ; immunology ; Child ; Child, Preschool ; Collagen Type IV ; analysis ; Cytoskeletal Proteins ; analysis ; Epithelial Cells ; chemistry ; metabolism ; Female ; Fluorescent Antibody Technique, Indirect ; Focal Adhesion Kinase 1 ; Focal Adhesion Protein-Tyrosine Kinases ; Granuloma ; pathology ; physiopathology ; Humans ; Immunohistochemistry ; Infant ; Keratins ; analysis ; Laminin ; analysis ; Lipopolysaccharide Receptors ; analysis ; Male ; Middle Aged ; Protein-Tyrosine Kinases ; analysis ; Proto-Oncogene Proteins c-kit ; analysis ; Serine Endopeptidases ; analysis ; Skin ; chemistry ; pathology ; physiopathology ; Stem Cell Factor ; analysis ; Trans-Activators ; analysis ; Tryptases ; beta Catenin