OBJECTIVETo investigate the expression and gene mutation of cluster of differentiation 9 (CD9) in the pathway of the mineral powder induced malignant transformation in immortalized human bronchial epithelial cells (BEAS-2B) in Gejiu.

METHODSBEAS-2B cells served as the control group and its malignant transformation cells induced by mineral powder in Gejiu were considered as experiment group. The expression of CD9 protein in 20 bottles of BEAS-2B cells and 20 bottles of malignant transformation cells was evaluated by immunocytochemistry. The mRNA expression of CD9 in 10 bottles of BEAS-2B cells and 10 bottles of malignant transformation cells was examined by reverse transcriptase polymerase chain reaction (RT-PCR). Gene mutation was detected in the products of RT-PCR by DNA sequencing.

RESULTSThere was significant difference between the expression of CD9 protein in BEAS-2B cells (100%, 20/20) and that in its malignant transformation cells (35%, 7/20 P < 0.01). The expression of CD9 mRNA in BEAS-2B cells 0.91 +/- 0.09 was significantly higher than that in its malignant transformation cells (0.34 +/- 0.14) (P < 0.01). Two point mutation of CD9 gene was detected in the malignant transformation cells of BEAS-2B by DNA sequencing. The change of G-->T in the base of 231 led to the change of Gln-->His in the amino acids of 40. The change of T-->A in the base of 119 led to the change of Val-->Asp in the amino acids of 3.

CONCLUSIONThe absence or down-regulation of CD9 expression and point mutation in the malignant transformation cells of BEAS-2B may play a considerable role in the pathway of the malignant transformation in the BEAS-2B cells induced by mineral powder in Gejiu.

Bronchi ; pathology ; Cell Line ; Cell Transformation, Neoplastic ; drug effects ; genetics ; Dust ; Epithelial Cells ; drug effects ; metabolism ; pathology ; Gene Expression Regulation ; drug effects ; Humans ; Lung Neoplasms ; chemically induced ; genetics ; metabolism ; pathology ; Mining ; Mutation ; drug effects ; Tetraspanin-29 ; genetics ; metabolism

OBJECTIVETo study the expression of neutral endopeptidase (CD10) and motility-related protein-1 (CD9) in malignant melanoma and their clinical significance.

METHODSImmunohistochemical study for CD10 and CD9 using Streptavidin-biotin complex technique was carried out in 48 cases of primary cutaneous malignant melanoma (CMM), 23 cases of metastatic melanoma and 23 cases of benign nevus.

RESULTSThe positivity rate of CD10 was highest in metastatic melanoma and lowest in benign nevus (P < 0.01). In contrast, the positivity rate of CD9 in metastatic melanoma was lower than that in CMM (P < 0.05). The expression of CD9 was inversely correlated with that of CD10 in malignant melanoma (CMM: r = -0.40, P = 0.005; metastatic MM: r = -0.44, P = 0.034). The expression of CD10 and CD9 in CMM also correlated with tumor histology, Clark's level of invasion and presence of nodal metastasis. A similar relationship was also observed for CD10 and CD9 expression in stromal fibroblasts of CMM (r = -0.43, P = 0.007).

CONCLUSIONSCD10 and CD9 expression correlates with the invasiveness and metastatic potential of malignant melanoma; both factors may demonstrate a counteracting effect. These two markers have potential implications in prognostic assessment of CMM. Stromal fibroblasts may also play an important role in the progression of CMM.

Antigens, CD ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Melanoma ; metabolism ; pathology ; secondary ; Membrane Glycoproteins ; metabolism ; Neoplasm Invasiveness ; Neoplasm Staging ; Neprilysin ; metabolism ; Skin Neoplasms ; metabolism ; pathology ; secondary ; Tetraspanin-29

OBJECTIVETo clone and identify gastric cancer-related genes and explore the possible pathogenic mechanism of gastric cancer.

METHODSThe differentially expressed cDNA bands were isolated by fluorescent mRNA differential display in gastric cancer specimens, matched normal gastric mucosa and premalignant lesions. The motility-related protein-1 (MRP-1/CD9) gene was one of the down-regulated genes. MRP-1/CD9 gene expression in different kinds of gastric tissue was analyzed by Northern blot and reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSMRP-1/CD9 expression was down-regulated in all gastric cancer tissues. Northern blot analysis confirmed this differential expression. RT-PCR analysis showed that the MRP-1/CD9 gene expression was much lower in gastric cancers(0.31+/-0.18) than in the matched normal gastric tissue (0.49+/-0.24) and in the premalignant lesions (0.47+/-0.18) (P<0.05), and its expression in intestinal type gastric cancer (0.38+/-0.16) was higher than that in diffuse type gastric cancer (0.22+/-0.17) (P<0.05).

CONCLUSIONThe MRP-1/CD9 gene expression was down-regulated in gastric cancer, its expression was probably related to the carcinogenesis and histology types of gastric cancer.

Antigens, CD ; genetics ; Blotting, Northern ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Membrane Glycoproteins ; genetics ; Precancerous Conditions ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Stomach Neoplasms ; genetics ; Tetraspanin-29

OBJECTIVE: To study the expression of SKP2 and MRP-1/CD9 protein in glottic cancer and adjacent tissues, and to analyze its significance for a safe surgical margin. METHOD: Thirty-eight cases of glottic squamous cell carcinoma were studied for its cancer tissue, tissue 2 mm, 5 mm, and 10 mm away from cancer, and 10 cases of vocal cord polyp were served as control. SKP2 and MRP-1/CD9 protein were examined by immunohistochemical method. RESULT: The positive expression of SKP2 proteins decreased in sequence of polyp mucosa, those adjacent to carcinoma (10 mm, 5 mm, 2 mm ) and cancer tissue, and there was significant difference between them (P < 0.05); On the contrary, the positive expression of the MRP-1/CD9 proteins increased in sequence of polypous mucosa, those adjacent to carcinoma (10 mm, 5 mm, 2 mm) and cancer tissue,and there was significant difference between them (P < 0.05). CONCLUSION SKP2 and MRP-1/CD may act as the reference index for judging the biological specialty of LSCC. It is appropriate to regard 5 mm or above 5 mm away from tumors as a safe margin for surgical treatment of glottic carcinoma.
Adult ; Aged ; Antigens, CD ; metabolism ; Female ; Glottis ; pathology ; Humans ; Laryngeal Neoplasms ; metabolism ; pathology ; Male ; Membrane Glycoproteins ; metabolism ; Middle Aged ; Neoplasm Staging ; Neoplasms, Squamous Cell ; metabolism ; pathology ; S-Phase Kinase-Associated Proteins ; metabolism ; Tetraspanin 29

OBJECTIVETo study the immunophenotype and chromosome karyotype characteristics of leukemic stem cells (LSC) in Uyghur leukemia pediatric patients.

METHODSThe morphological features of LSC in culture in vitro was observed by flow cytometry. The immunophenotype was assessed by detective flow cytometry. The chromosome karyotype was analyzed by R-banding technique.

RESULTSThe LSC showed suspended floating colonies growing in the culture medium, and grew well and proliferated constantly in culture over 8 months. Among the 13 children with AML, there were 10 CD34(+)CD38(-)CD123(+) and CD33(+) cases, 10 CD44(+) cases, 10 CD96(+) cases, and 5 CD90(+) cases. Among the 13 children with B-ALL, there were 6 CD34(+)CD20(-)CD19(+) cases, 7 CD9(+) cases, and 5 CD123(+) cases. Among the 9 children with acute T lymphoblastic leukemia (T-ALL), there were 5 CD34(+)CD7(-) and CD90(+) cases, and 4 CD123(+) cases. Among the 13 cases of AML, 5 cases showed chromosome translocation t(15;17), one case chromosome translocation t(8;21), and 7 cases showed no chromosome karyotype abnormality. Among the 22 ALL cases, there were chromosome translocation t(12;21) in 1 case, t(9;22) in 3 case, hyperdiploid in 2 cases, and 16 cases without karyotype abnormalities. Twenty-nine children received induction remission therapy. Among them, 12 died, including 9 CD96(-)positive cases and 3 CD96(-)negative cases, with a statistically significant difference (P < 0.05).

CONCLUSIONSThe LSC of Uyghur leukemia pediatric patients in Xinjiang express CD9 and CD19 in ALL, and express CD123 and CD90 simultaneously in ALL and AML. The expression of CD96 is one of factors of poor prognosis.

Adolescent ; Antigens, CD ; metabolism ; Antigens, CD19 ; metabolism ; Child ; China ; ethnology ; Diploidy ; Humans ; Immunophenotyping ; Interleukin-3 Receptor alpha Subunit ; metabolism ; Karyotyping ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; immunology ; pathology ; Neoplastic Stem Cells ; immunology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; immunology ; pathology ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; immunology ; pathology ; Remission Induction ; Tetraspanin-29 ; metabolism ; Thy-1 Antigens ; metabolism ; Translocation, Genetic

OBJECTIVETo study the clinicopathologic features and differential diagnosis of splenic lymphangioma.

METHODSEighteen cases of splenic lymphangioma were retrieved from the pathology archives during the period between January 1990 to December 2005. The clinicopathologic features were analyzed. Immunohistochemical study was performed on the paraffin sections of 16 cases.

RESULTSThe age of the patients ranged from 9 to 72 years (median = 40 years). Thirteen patients were males and 5 were females. Clinically, the tumor could be asymptomatic or present with abdominal symptoms and hypersplenism. Follow-up information was available in 13 patients (72.2%) and the duration varied from 5 months to 15 years. All 13 patients had an uneventful clinical course, with no evidence of residual disease, local recurrence or metastasis. Gross examination showed splenic enlargement. The tumor appeared as cystic (8/18), solid (5/18) or honeycomb mass (5/18), either solitary (5/18) or multifocal (13/18). Histologically, splenic lymphangioma could be subclassified as cavernous (9/18), cystic (5/18) or mixed (4/18). Immunohistochemical study showed that the positivity rates for CD9 and D2-40 were 100% and 43.8% respectively.

CONCLUSIONSSplenic lymphangioma is a rarely encountered entity that can be misdiagnosed as a splenic hemangioma. A definite diagnosis depends on pathologic examination.

Adult ; Aged ; Antibodies, Monoclonal ; metabolism ; Antibodies, Monoclonal, Murine-Derived ; Antigens, CD ; metabolism ; Biomarkers, Tumor ; metabolism ; Child ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Hemangioma ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Lymphangioma ; metabolism ; pathology ; surgery ; Lymphangioma, Cystic ; metabolism ; pathology ; surgery ; Male ; Membrane Glycoproteins ; metabolism ; Middle Aged ; Splenectomy ; Splenic Neoplasms ; metabolism ; pathology ; surgery ; Tetraspanin-29

BACKGROUND: CD9, a member of the tetraspanin superfamily, is a tumor suppressor in many malignancies. The aim of this study was to evaluate the immunohistochemical expression of CD9 in colorectal carcinomas (CRCs) and determine clinicopathological and prognostic significance of its expression. METHODS: The CD9 expression status of 305 CRCs was evaluated using a semi-quantitative scoring system in tumor cells (T-CD9) and immune cells (I-CD9) by classifying the results as high and low expression. RESULTS: High T-CD9 (T-CD9 [+]) expression was detected in 175 samples (57.6%) and high I-CD9 (I-CD9 [+]) expression was detected in 265 samples (86.9%). Using Kaplan-Meier survival analysis, the T-CD9 (+) group showed a tendency for better disease-free survival (DFS) (p = .057). In left-sided tumors, DFS was significantly longer in the T-CD9 (+) group (p = .021) but no statistical significance was observed with right-sided tumors (p = .453). I-CD9 (+) CRCs significantly correlated with well/moderately differentiation (p = .014). In Kaplan-Meier analysis, the I-CD9 (+) group had a tendency towards worse DFS compared to the I-CD9 (–) group (p = .156). In combined survival analysis of T-CD9 and I-CD9, we found that the longest DFS was among patients in the T-CD9 (+)/I-CD9 (–) group, whereas the T-CD9 (–)/I-CD9 (+) group showed the shortest DFS (p = .054). CONCLUSIONS: High expression of T-CD9 was associated with a favorable DFS, especially in left-sided CRCs. Combined evaluation of T-CD9 and I-CD9 is required to determine the comprehensive prognostic effect of CD9 in CRCs.
Antigens, CD9 ; Colorectal Neoplasms* ; Disease-Free Survival ; Humans ; Kaplan-Meier Estimate ; Prognosis

LR11, also known as SorLA or SORL1, is a type-I membrane protein from which a large extracellular part, soluble LR11 (sLR11), is released by proteolytic shedding on cleavage with a disintegrin and metalloproteinase 17 (ADAM17). A shedding mechanism is presumed to have a key role in the functions of LR11, but the evidence for this has not yet been demonstrated. Tetraspanin CD9 has been recently shown to regulate the ADAM17-mediated shedding of tumor necrosis factor-alpha and intercellular adhesion molecule-1 on the cell surface. Here, we investigated the role of CD9 on the shedding of LR11 in leukocytes. LR11 was not expressed in THP-1 monocytes, but it was expressed and released in phorbol 12-myristate 13-acetate (PMA)-induced THP-1 macrophages (PMA/THP-1). Confocal microscopy showed colocalization of LR11 and CD9 proteins on the cell surface of PMA/THP-1. Ectopic neo-expression of CD9 in CCRF-SB cells, which are LR11-positive and CD9-negative, reduced the amount of sLR11 released from the cells. In contrast, incubation of LR11-transfected THP-1 cells with neutralizing anti-CD9 monoclonal antibodies increased the amount of sLR11 released from the cells. Likewise, the PMA-stimulated release of sLR11 increased in THP-1 cells transfected with CD9-targeted shRNAs, which was negated by treatment with the metalloproteinase inhibitor GM6001. These results suggest that the tetraspanin CD9 modulates the ADAM17-mediated shedding of LR11 in various leukemia cell lines and that the association between LR11 and CD9 on the cell surface has an important role in the ADAM17-mediated shedding mechanism.
ADAM Proteins/*metabolism ; Antigens, CD9/genetics/*metabolism ; Cell Line, Tumor ; Humans ; LDL-Receptor Related Proteins/genetics/*metabolism ; Leukocytes/*metabolism ; Macrophages/metabolism ; Membrane Transport Proteins/genetics/*metabolism ; Proteolysis

BACKGROUND: In acute leukemia patients, several successful methods of expression profiling have been used for various purposes, i.e., to identify new disease class, to select a therapeutic target, or to predict chemo-sensitivity and clinical outcome. In the present study, we tested the peripheral blood of 47 acute leukemia patients in an attempt to identify differentially expressed genes in AML and ALL using a Korean-made 10K oligo-nucleotide microarray. METHODS: Total RNA was prepared from peripheral blood and amplified for microarray experimentation. SAM (significant analysis of microarray) and PAM (prediction analysis of microarray) were used to select significant genes. The selected genes were tested for in a test group, independently of the training group. RESULTS: We identified 345 differentially expressed genes that differentiated AML and ALL patients (FWER < 0.05). Genes were selected using the training group (n=35) and tested for in the test group (n=12). Both training group and test group discriminated AML and ALL patients accurately. Genes that showed relatively high expression in AML patients were deoxynucleotidyl transferase, pre-B lymphocyte gene 3, B-cell linker, CD9 antigen, lymphoid enhancer-binding factor 1, CD79B antigen, and early B-cell factor. Genes highly expressed in ALL patients were annexin A 1, amyloid beta (A4) precursor protein, amyloid beta (A4) precursor-like protein 2, cathepsin C, lysozyme (renal amyloidosis), myeloperoxidase, and hematopoietic prostaglandin D2 synthase. CONCLUSION: This study provided genome wide molecular signatures of Korean acute leukemia patients, which clearly identify AML and ALL. Given with other reported signatures, these molecular signatures provide a means of achieving a molecular diagnosis in Korean acute leukemia patents.
Amyloid ; Antigens, CD79 ; Antigens, CD9 ; B-Lymphocytes ; Cathepsin C ; Diagnosis ; DNA Nucleotidylexotransferase ; Gene Expression* ; Genome ; Humans ; Leukemia* ; Leukemia, Myeloid, Acute ; Lymphoid Enhancer-Binding Factor 1 ; Muramidase ; Peroxidase ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Precursor Cells, B-Lymphoid ; Prostaglandin D2 ; RNA ; Transcriptome*

This study investigated the expression and clinicopathological significance of CD9 in gastrointestinal stromal tumor (GIST). Immunohistochemistry staining for CD9 was performed on tumor tissues from 74 GIST patients. The correlation with clinicopathological features, risk classification and prognosis was analyzed. CD9-positive staining comprised 59.5% (44/74) of the GIST patients. The CD9-positive expression rate of the sample was significantly associated with diameter (P = 0.028), mitotic counts (P = 0.035), risk classification (P = 0.018) and three-year recurrence-free survival (RFS) (P < 0.001). Cox proportional hazards regression (HR = 0.352; P = 0.015) showed that CD9 is an independent factor for post-operative RFS. The subgroup analysis showed that CD9 expression in gastric stromal tumor (GST) is significantly associated with diameter (P = 0.031), risk classification (P = 0.023) and three-year RFS (P = 0.001). The Cox proportional hazards regression (HR = 0.104; P = 0.006) also showed that CD9 is an independent factor for RFS of GST. However, CD9 expression does not have a statistically significant correlation with clinicopathological features, risk classification, and prognosis in non-GST. In conclusion, CD9 expression in GIST appears to be associated with the recurrence and/or metastasis of GIST patients, especially in GST, which may indicate the important role of CD9 in the malignant biological behavior and prognosis of GST.
Adult ; Aged ; Aged, 80 and over ; Antigens, CD9/*genetics/*metabolism ; Disease-Free Survival ; Female ; Gastrointestinal Neoplasms/metabolism/mortality/*pathology ; Gastrointestinal Stromal Tumors/metabolism/mortality/*pathology ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Risk Factors