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CD10, actin, and vimentin expression in breast phyllodes tumors correlates with tumor grades of the WHO grading system.

The discrimination of borderline from malignant primary breast phyllodes (PT) tumor is still unclear. We studied 22 PT cases to investigate the immunohistochemical expression (staining of stromal CD10, SMA [smooth muscle actin], and vimentin) as well as the features of focal glandular atypia to determine whether these correlated with the histopathologic grading system. In our results, the stromal staining of CD10 was positive in 4 of 6 malignant and 2 of 5 borderline PT cases, but negative in all benign PT cases. Stromal actin and intraglandular vimentin-expressive tumor cells were found in 5 of 6 malignant PT cases but not in borderline and benign PT cases. There is a significant difference in the panel of stromal CD10, actin, and vimentin expression between borderline and malignant PT (p<0.05). Besides, the progression of malignant potential breast phyllodes tumor may cause glandular epithelium atypia with loss of polarity.

Actins↗

Assessment of CD10 in the diagnosis of small B-cell lymphomas: a multiparameter flow cytometric study.

We evaluated the usefulness of multiparameter flow cytometry with cluster analysis in the diagnosis of a series of 100 well-characterized small B-cell lymphomas (SBCLs). The histologic diagnoses in the 100 cases were follicular lymphoma (FL) in 58, marginal zone lymphoma (MZL) in 17, small lymphocytic lymphoma in 15, and mantle cell lymphoma (MCL) in 10. Of the 58 FLs, 57 were CD10 positive (98% sensitivity). The 1 negative case was unusual in that it occurred in the small intestine. However; architectural, cytologic, and immunohistochemicalfeatures were diagnostic of FL. Of 42 other SBCLs, 2 were CD10+ (95% specificity); 1 was a CD5+/cyclin D1 + MCL, and the other was an extranodal MZL. We found that assessment of CD10 expression using multiparameter flow cytometry with cluster analysis is highly sensitive and specific for the diagnosis of FL, validating its usefulness in situations in which adequate tissue is not available for definitive histologic diagnosis.

Adult↗

Prognostic significance of the CD10+CD19+CD34+ B-progenitor immunophenotype in children with acute lymphoblastic leukemia: a report from the Children's Cancer Group.

Leukemic cells from most patients with B-lineage acute lymphoblastic leukemia (ALL) appear to originate from normal B-lymphocyte precursors. The earliest B-cell progenitors coexpress the antigens CD10, CD19, or CD34 on their cell surfaces. In a large cohort of 2028 children with ALL, we compared treatment outcomes of a subset of B-lineage ALL patients with CD10+CD19+CD34+ immature B-progenitor leukemia (BPL) to the treatment outcomes of the remaining CD19+ B-lineage ALL patients. Pediatric B-lineage ALL cases enrolled on risk-adjusted ALL treatment protocols of the Children's Cancer Group were immunophenotypically classified as BPL or non-BPL. Patients were stratified further into age groups of > or = 1 year and <12 months. Event-free survival (EFS) outcomes were calculated by standard life table methods. BPL patients in both age groups generally had more favorable presenting characteristics than non-BPL controls. Within the age group of > or = 1 year, BPL patients had a slightly better EFS outcome than non-BPL patients, with 3-year estimates of 83.9% (SD = 1.1%) vs. 78.8% (SD = 1.8%), respectively (P = 0.10). Infants with BPL, representing one-fifth of the total infant patient population, had a significantly better EFS outcome than infants with non-BPL (three-year EFS: 82.4%, SD = 9.2% vs. 34.4%, SD = 5.9%, P = 0.006). In univariate analyses, the relative hazard rate (RHR) was 3.73 for non-BPL vs BPL and this marked difference in EFS outcome was maintained at 5 years of follow-up. The favorable prognostic influence of the BPL immunophenotype for infants remained significant in multivariate analyses with an RHR of 2.72 for non-BPL vs BPL (P = 0.05). CD10+CD19+CD34+ immature B-progenitor immunophenotype is associated with favorable characteristics for children with ALL and identifies a subset of infants who achieve favorable EFS outcomes.

Adult↗

Low-grade B-cell lymphoma with coexpression of both CD5 and CD10. A report of 3 cases.

The coexpression of CD5 and CD10 has previously been reported in cases of intermediate- and high-grade lymphomas and in precursor B cells in normal or regenerating bone marrow. We report 3 cases of low-grade B-cell lymphoma that were found to coexpress CD5 and CD10 at the time of initial diagnosis. The first case was classified as small lymphocytic lymphoma; the second as follicle center lymphoma, follicular grade 1; and the third as small B-cell lymphoma otherwise not specified. Currently, the clinical implication of the coexpression of CD5 and CD10 is not known. We describe this finding to highlight the difficulty that may be encountered in classifying lymphomas in cases where this coexpression is present.

Aged↗

An otherwise typical case of non-Japanese hairy cell leukemia with CD10 and CDw75 expression: response to cladaribine phosphate therapy.

Hairy cell leukemia (HCL) in Western patients typically expresses CD19, CD20, CD11c, CD25, HLA-DR, and IgG/lambda and lacks expression of CD5 and CD10. The immunophenotype is in contrast to Japanese HCL which typically expresses CD5 and CD10. Western and Japanese HCL also differ in their clinical presentation and response to treatment with alpha-interferon. We report a case of non-Japanese HCL which presented typically with pancytopenia; however, the immunophenotype was atypical with expression of CD10 and CDw75. CDw75 expression has not previously been described in either Japanese or non-Japanese HCL. The patient achieved a marked partial pathologic response and complete clinical response to treatment with cladaribine phosphate.

Antigens, CD↗

CD10 expression in cultured human osteoblast-like cells.

Morphological features, bone nodule formation and alkaline phosphatase activity are currently used to identify osteoblasts. CD10 (cALLa antigen) is a glycoprotein with endopeptidase activity and it is present on the surface of many cell types. We have studied the expression of CD10 in osteoblast-like cells by immunocytochemistry and flow cytometry in order to identify other markers of the osteoblast lineage. We isolated osteoblast-like cells from specimens obtained in the course of oral surgery. Expression of the cALLa antigen (CD10) may also be an indicator of the osteoblast phenotype.

Alkaline Phosphatase↗

CD10 in diffuse uterine leiomyomatosis: a case report along with a few comments on histogenesis.

Diffuse uterine leiomyomatosis (DUL) is a rare entity with an unknown etiopathogenesis. A 24 years old female presented with abdominal discomfort and menorrhagia. Clinical and ultrasonographic examination revealed an enlarged uterus. The hysterectomy specimen showed a symmetrically enlarged uterus with a bosselated external surface. The cut surface showed multiple nodules of varying sizes diffusely involving the myometrium. Microscopically, the nodules were leiomyomas of varying degrees of cellularity. Some of the leiomyomas showed an increased vascularity either in the form of congeries of blood vessels with a lobular arrangement or occasionally as foci of 2-3 vessels. The vessels were surrounded by whorls of spindle cells. On immunohistochemistry the leiomyomas expressed vimentin, smooth muscle actin (SMA), desmin and CD10: the cells whorling around the blood vessels expressed vimentin, SMA and focally desmin and were negative for CD10 and HMB-45. The aim of this paper is to document that CD10 is expressed in diffuse uterine leiomyomatosis and discuss the histogenesis of DUL.

Adult↗

High levels of functional endopeptidase 24.11 (CD10) activity on human thymocytes: preferential expression on immature subsets.

Although it is now well established that cells of the immune system express most of the exopeptidases described so far, little information is available concerning the identification and the characterization of the peptidases associated with the surface of human thymocytes. In the present study we have focused on CD10 expression on thymocytes using both FACS and enzymatic analysis. Unfractionated intact human thymocytes were shown to express significant levels of CD10-specific enzymatic activity, as assessed by the hydrolysis of the neutral endopeptidase (NEP) substrate Suc-Ala-Ala-Phe-pNA and of D-Ala2-Leu-enkephalin, a typical NEP substrate. CD10 activity was abolished by specific NEP inhibitors, including thiorphan, retrothiorphan and phosphoramidon. Moreover, high performance liquid chromatography (HPLC) analysis showed that intact thymocytes and purified NEP hydrolysed thymopentin, a thymic factor known to induce the maturation of prothymocytes into thymocytes. Finally, CD 10/NEP was preferentially associated with CD3- CD3low and immature CD4- CD8- thymocytes. The data demonstrate for the first time that human thymocytes express functional NEP and suggest a role for this enzyme in the maturation of human thymocytes.

CD3 Complex↗

Individual CD34+CD38lowCD19-CD10- progenitor cells from human cord blood generate B lymphocytes and granulocytes.

Identification of human hematopoietic stem cells and analysis of molecular mechanisms regulating their function require biological assays that permit differentiation in all hematopoietic lineages simultaneously. In this study, we established conditions that permit the joint expression of the B-lymphoid and myeloid potential from cord blood-derived CD34+CD38lowCD19-/CD10- primitive progenitors that lack B-specific markers and transcripts. When cocultured during 6 weeks with the murine stromal cells MS-5 in the absence of exogenous human cytokines, CD34+CD38low-CD19-CD10- cells generated a high number of CD19+ B cells. Virtually all of these cells expressed a CD34-CD10+- CD19+cIgM- phenotype of late pro-B cells and transcripts of Pax-5, lambda-like, and mu chain were detected. We further show that 7% of CD34+CD38lowCD19- cells from cord blood, when grown individually with MS-5 cells, generated both CD19+ and CD11b+ cells after 6 weeks. Efficient B-cell differentiation was also observed in vivo after transplantation of human cord blood-derived unfractionated mononuclear cells or CD34+CD19+CD10- cells into immune-deficient mice. In contrast to the in vitro situation, all stages of B-cell differentiation were observed in vivo, including pro-B, pre-B, and sIgM+ B cells. Interestingly, human progenitors with the ability to differentiate along both B-lymphoid and granulocytic pathways were also detected among human CD34+CD38low cells in the marrow of chimeric mice 6 to 7 weeks after transplantation. Both in vitro and in vivo systems will offer an invaluable tool to further identify the lymphoid and myeloid potentialities of primitive progenitor cells isolated from fetal as well as adult human hematopoietic tissues and characterize stromal-derived signals that regulate their function.

ADP-ribosyl Cyclase↗

CD5-negative, CD10-negative small B-cell leukemia: variant of chronic lymphocytic leukemia or a distinct entity?

CD5- and CD10-negative chronic lymphocytic leukemias are quite uncommon as compared to the CD5-positive CLL. We reviewed 250 sequential cases of peripheral blood lymphocytosis to characterize cases of small B-cell lymphoproliferative disorders, submitted with a clinical diagnosis of chronic lymphocytic leukemia exhibiting a non-classic immunophenotypic profile. Six cases of CD5-, CD10-negative chronic lymphocytic leukemias and no tissue involvement were identified that revealed high-density surface-membrane immunoglobulin and CD20 expression, with variable expression of CD11c, CD23, and CD25. Most had a profound leukocytosis (mean WBC 180 x 10(9)/L) with proliferation of mature-appearing lymphocytes. Subsequent bone marrow biopsies showed diffuse infiltration by neoplastic cells in all evaluated patients. The clinical course appeared indolent, with follow-up revealing three patients alive (survival time 38-68 months), while two died of unrelated causes and one was lost to follow-up soon after diagnosis. These cases may represent somewhat unusual chronic lymphoproliferative disorders, with morphologic features and immunophenotypic profile not readily classifiable, but which are certainly atypical for classic chronic lymphocytic leukemia. Some of these features are reminiscent of those seen in marginal-zone lymphoma. However, it is most unusual for this known to be tissue-based disease to present primarily as leukemia rather than lymphoma.

Antigens, CD↗

PU.1 protein expression has a positive linear association with protein expression of germinal centre B cell genes including BCL-6, CD10, CD20 and CD22: identification of PU.1 putative binding sites in the BCL-6 promotor.

The transcription factor PU.1 has been shown to be crucial for the early stages of B cell development but its function at later stages of B cell development is less well known. We observed previously that PU.1 is expressed uniformly throughout the mature pre-plasma cell B cell population, the only exception being a subpopulation of germinal centre (GC) cells which showed exceptionally high expression of PU.1. This suggested that PU.1 may also have a role in GC B cell biology. To test this hypothesis and to screen for possible genes regulated by PU.1, we first evaluated semi-quantitatively the possible co-expression of PU.1 with proteins known to be upregulated or downregulated during GC B cell development. Normal lymphoid tissues and 255 B cell non-Hodgkin lymphomas of putative GC B cell origin were evaluated. PU.1 expression was positively associated with CD10 (p < 0.0001), CD20 (p = 0.043), CD22 (p = 0.005), CD79a (p = 0.024) and Bcl-6 (p < 0.0001) and negatively associated with cytoplasmic immunoglobulin light-chain expression (p = 0.036) in diffuse large B cell lymphoma. Identical or nearly identical associations were found in follicular lymphoma. Since CD20 is known to be partly regulated by PU.1 and putative PU.1-binding sites have been described in the regulatory regions of the CD22, CD79a and CD10 genes, we looked for putative PU.1 binding sites in the BCL6 promotor. Four such putative PU.1 binding sites were identified. Further analysis by gel-shift electromobility essay showed that PU.1 protein binds to three of the four putative binding sites in the BCL6 promotor. PU.1 and Bcl-6 were also found to be upregulated in centroblasts in the normal GC, but jointly downregulated in a subpopulation of centrocytes. Our findings support the contention that PU.1 may also have an important role in GC B cell development.

Antigens, CD↗

Translocation (2;14)(p13;q32) in CD10+ ;CD13+ acute lymphatic leukemia.

The rare t(2;14)(p13;q32) was previously described in the three pediatric patients with acute lymphatic leukemia. In these cases this abnormality was found at diagnosis, manifested the sole chromosomal abnormality, and was associated with a favorable prognosis. We here describe three cases of leukemia where such translocations were found at relapse, were associated in two of the cases with additional known characteristic chromosomal aberration, and were associated with a grave prognosis. Interestingly enough, the malignant cells of all three patients shared the same surface antigens: CD34, HLA DR, CD10, CD20, and the myeloid marker CD13. The leukemic clone exhibiting t(2;14) probably evolved from a t(1;19)6q- pre-B acute lymphatic leukemia in one of the cases, and from a chronic phase Ph1 chromosome in another. The significance of the translocation and the coexistence of CD10 and CD13 on the same cell are discussed.

Adolescent↗

In vitro depletion of clonogenic cells in adult acute lymphoblastic leukemia with a CD10 (anti-cALLA) monoclonal antibody.

A semi-solid medium colony assay was used in common acute lymphoblastic leukemia (cALL) to test growth inhibition of leukemic progenitors (CFU-L) after exposure to monoclonal antibodies (MoAbs) directed against CD10 and CD9 antigens. Peripheral or bone marrow cells from 15 patients were plated after exposure to various concentrations of ALB2, a CD10 cytotoxic MoAb, followed by complement lysis. CFU-L inhibition was complete (no residual colony) in 5 cases (33%), marked (greater than or equal to 95%) in 4 cases (27%), but only moderate (64% +/- 28) in 6 cases (40%). This inhibition was not related to the percentage of cALLA positive cells before exposure to MoAb. In addition, cells of 5 patients were exposed to BA1 (CD24) + complement. In these cases, the proportion of CFU-L inhibition was equal to or higher than with ALB2. In 3 cases, cells were exposed to an association of ALB2 and SB4 (CD19) MoAbs followed by complement lysis, with a marked inhibition (greater than or equal to 99%) in 2/3 cases. These observations give supplementary support to the use of several MoAbs directed against various antigens present at early stages of B differentiation.

Adolescent↗

Leukemia-specific serum from a child showing an immunofluorescent pattern distinct from J-5 monoclonal antibody directed for CD10 (common ALL antigen).

Leukemia-specific human antibody was detected in a child with acute lymphoblastic leukemia (ALL) treated with chemoimmunotherapy. Chemoimmunotherapy consists of standard chemotherapy and subcutaneous injections of irradiated ALL cells with a biological response modifier. This ALL-specific serum reacted in 60 out of 67 (89.5%) children with ALL and was not reactive with normal cells. Furthermore, this ALL-specific serum showed a different immunofluorescent pattern on dual staining as compared with J-5 monoclonal antibody directed for common ALL antigen (CALLA; CD10). J-5 did not block the reactivity of ALL-specific serum, and vice versa, when CD10-positive ALL cell lines were used as targets. These findings suggest the possibility that there exists an ALL-specific antigen(s) which is different from CALLA and that this antigen(s) elicits a tumor-specific antibody response.

Antibodies, Monoclonal↗

t(8;14)(q24;q32) in two patients with CD10-negative primary thyroid diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) with the 8q24 translocation is occasionally seen in the gastrointestinal tract, but has rarely been reported in the thyroid gland. We experienced two cases of primary thyroid DLBCL having t(8;14)(q24;q32). The immunophenotype and karyotype of Case 1 (66-year-old female) and Case 2 (70-year-old female) were: CD10-, CD20+, BCL-2+/add(13)(q34), t(8;14)(q24;q32) and CD10-, CD20-, CD79a+, BCL-2-/t(8;14)(q24;q32), respectively. Although long-term complete remission could be achieved in both of our patients by conventional chemotherapy with/without radiation therapy, accumulation of further such cases is necessary to develop a standard treatment protocol and also to elucidate the pathogenesis of t(8;14)(q24;q32)-positive primary thyroid DLBCL.

Aged↗

Adult precursor B-ALL with BCR/ABL gene rearrangements displays a unique immunophenotype based on the pattern of CD10, CD34, CD13 and CD38 expresssion.

The Philadelphia chromosome (Ph+) reflects a balanced reciprocal translocation between the long arms of chromosomes 9 and 22 [t(9;22)(q34;q11.2] involving the BCR and ABL genes. At present, detection of BCR/ABL gene rearrangements is mandatory in precursor-B-ALL patients at diagnosis for prognostic stratification and treatment decision. In spite of the clinical impact, no screening method, displaying a high sensitive and specificity, is available for the identification of BCR/ABL+ precursor-B-ALL cases. The aim of the present study was to explore the immunophenotypic characteristics of precursor B-ALL cases displaying BCR/ABL gene rearrangements using multiple stainings analyzed by quantitative flow cytometry in order to rapidly (<1 h) identify unique phenotypes associated with this translocation. From the 82 precursor-B-ALL cases included in the study 12 displayed BCR/ABL gene rearragements, all corresponding to adult patients, four of which also displayed DNA aneuploidy. Our results show that BCR/ABL+ precursor B-ALL cases constantly displayed a homogeneous expression of CD10 and CD34 but low and relatively heterogeneous CD38 expression, together with an aberrant reactivity for CD13. In contrast, this unique phenotype was only detected in three out of 70 BCR/ABL cases. Therefore, the combined use of staining patterns for CD34, CD38 and CD13 expression within CD10-positive blast cells is highly suggestive of BCR/ABL gene rearrangements in adults with precursor B-ALL.

Adult↗

Monoclonal antibodies recognizing CD5, CD10 and CD23 in formalin-fixed, paraffin-embedded tissue: production and assessment of their value in the diagnosis of small B-cell lymphoma.

AIMS: Assessment of the expression of antigens CD5, CD10 and CD23 can be of value in the differential diagnosis of small B-cell lymphoma. Correct subclassification is important since optimal treatment regimes differ between the subtypes. The aim of this study was to generate monoclonal antibodies recognizing these antigens in paraffin-embedded tissue and to assess their efficacy using a panel of cases of small B-cell lymphoma of various subtypes. METHODS AND RESULTS: For each antibody synthetic recombinant protein and conventional murine hybridoma technology was employed. Monoclonal antibodies effective in formalin-fixed, paraffin-embedded tissue were successfully generated, designated NCL-CD5-4C7, NCL-CD10-270 and NCL-CD23-1B12, respectively. A series of 58 cases of small B-cell lymphoma including examples of each subtype (lymphocytic, follicle centre cell, mantle cell, marginal zone and lymphoplasmacytoid) was assembled and immunostaining for the respective antigens carried out using the monoclonal antibodies produced. Our results indicate that the antibodies are specific for their respective antigens and give the predicted phenotypic profile in the small B-cell lymphoma subtypes. CONCLUSIONS: These novel monoclonal antibodies may be of value in routine diagnostic practice.

Animals↗

Human pluripotent and progenitor cells display cell surface cluster differentiation markers CD10, CD13, CD56, and MHC class-I.

Each year millions of people suffer tissue loss or end-stage organ failure. While allogeneic therapies have saved and improved countless lives, they remain imperfect solutions. These therapies are limited by critical donor shortages, long-term morbidity, and mortality. A wide variety of transplants, congenital malformations, elective surgeries, and genetic disorders have the potential for treatment with autologous stem cells as a source of HLA-matched donor tissue. Our current research is aimed at characterizing cell surface cluster differentiation (CD) markers on human progenitor and pluripotent cells to aid in isolating comparatively purified populations of these cells. This study examined human pluripotent and progenitor cells isolated from fetal, mature, and geriatric individuals for the possible presence of 15 CD markers. The response to insulin and dexamethasone revealed that the cell isolates were composed of lineage-committed progenitor cells and lineage-uncommitted pluripotent cells. Flow cytometry showed cell populations positive for CD10, CD13, CD56, and MHC Class-I markers and negative for CD3, CD5, CD7, CD11b, CD14, CD15, CD16, CD19, CD25, CD45, and CD65 markers. Northern analysis revealed that CD13 and CD56 were actively transcribed at time of cell harvest. We report the first identification of CD10, CD13, CD56, and MHC Class-I cell surface antigens on these human cells.

Adult↗