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CD10 immunostaining of bile canaliculi in liver biopsies: change of staining pattern with the development of cirrhosis.

AIMS: This study was prompted by published observations concerning the absence of normal bile canalicular CD10 staining in some cases of primary liver cell carcinoma. Our aim was to investigate the possibility that this loss of staining occurs prior to the development of cancer. METHODS AND RESULTS: The study comprised 164 liver biopsies, including 96 from patients with hepatitis C infection of various grades and stages including nine cases with cirrhosis, 24 other cases of cirrhosis of other aetiology, five cases of primary liver carcinoma, 12 cases of metastatic carcinoma, as well as biopsies with a variety of other liver diseases. CD10 was demonstrated in paraffin sections using the avidin-biotin immunoperoxidase technique. In hepatitis C cases, a significant loss of the canalicular pattern was seen in four out of 41 (10%) biopsies with stages 0-1 compared with 25 out of 55 (45%) with stages 2-6 (P < 0.001). There was also a significant difference (P < 0.001) between biopsies with stage 2-3 and those with stage 4-6, where marked pattern loss was seen in 9/37 (24%) and 16/18 (89%), respectively. Marked loss of the pattern was also seen in 16 out of the 24 (67%) other cirrhotic biopsies, as well as in cases with severe lobular inflammation and cholestasis and liver cell dysplasia and carcinoma. In hepatitis C biopsies, no relationship was noted between the reduction in the canalicular pattern and the necroinflammatory score. CONCLUSIONS: CD10-stained bile canalicular pattern in liver biopsies is preserved in cases with mild fibrosis and inflammation, but it becomes increasingly reduced with the advance of fibrosis or the presence of severe lobular inflammation or extensive metastases. Further investigations into the relationship between the changes in CD10 staining pattern and liver function tests may be useful in explaining test results.

Adolescent↗

HepPar1, MOC-31, pCEA, mCEA and CD10 for distinguishing hepatocellular carcinoma vs. metastatic adenocarcinoma in liver fine needle aspirates.

OBJECTIVE: To investigate immunohistochemical staining of hepatocyte paraffin-1 (HepPar1), alpha-fetoprotein (AFP), polyclonal carcinoembryonic antigen (pCEA), monoclonal CEA (mCEA), MOC-31 and CD10 for differential diagnosis of hepatocellular carcinoma (HCC) from metastatic adenocarcinoma (MA) on fine needle aspiration biopsy (FNAB). STUDY DESIGN: Fifty-one archival, paraffin-embedded FNAB cell blocks, representing 18 HCCs and 33 MAs, were immunostained with antibodies for AFP, CD10, pCEA, mCEA, HepPar1 and MOC-31. RESULTS: HepPar1, AFP, canalicular pCEA and CD10 were positive in 78% (14 of 18), 28% (5 of 18), 72% (13 of 18) and 35% (6 of 17) of cases of HCC, respectively. The 33 MAs were negative for immunostaining of the above antibodies except for one AFP-positive MA. Ninety-seven percent (31 of 32) of the MAs and 6% (1 of 17) of the HCCs were positive for MOC-31. Monoclonal CEA was immunoreactive on 82% (27 of 33) of the MAs and negative on all the HCCs. CONCLUSION: HepPar1 was the most sensitive marker for HCC, followed by canalicular staining for pCEA. For MA, MOC-31 was the most sensitive marker; mCEA was slightly less sensitive but more specific. We suggest using HepPar1, pCEA, CD10, MOC-31 and mCEA as a panel for distinguishing HCC from MA in liver FNAB.

Adenocarcinoma↗

CD10- pre-B acute lymphoblastic leukemia (ALL) is a distinct high-risk subgroup of adult ALL associated with a high frequency of MLL aberrations: results of the German Multicenter Trials for Adult ALL (GMALL).

Immunophenotyping disclosed CD10 negativity in 70 of 2408 cases of B-lineage acute lymphoblastic leukemia (ALL), although other criteria followed classification of pre-B ALL (eg, cytoplasmic immunoglobulin positivity). These blasts showed high myeloid antigen expression (60% CD65 positivity) and reacted with antibody 7.1 in 95% of the cases. MLL-AF4 fusion transcripts or an 11q23/MLL rearrangement or both were evident in 46 of 56 samples (82%). Although 83% of the patients achieved complete remission, the remission duration remained remarkably low: 141 days for MLL rearrangement-positive and 245 days for MLL rearrangement-negative CD10(-) pre-B ALL. Thus, the overall survival probability 3 years after diagnosis was 0.34 +/- 0.20 SE in MLL-rearrangement-negative versus 0.12 +/- 0.06 SE in MLL rearrangement-positive CD10- pre-B ALL. Our data identify CD10- cytoplasmic immunoglobulin-positive pre-B ALL as a rare (2.2%) but distinct immuno-subtype of adult ALL that is characterized by a high MLL rearrangement rate and a worse outcome.

Adolescent↗

B-cell lymphomas with coexpression of CD5 and CD10.

Coexpression of CD5 and CD10 is highly unusual in B-cell lymphomas and may pose a diagnostic challenge. We report 42 cases of B-cell lymphoma with simultaneous expression of CD5 and CD10. They made up approximately 0.4% of all B-cell lymphomas seen during the study period and included the following cases: large B-cell lymphoma (LBCL), 14 (33%); follicular lymphoma (FL), 10 (24%); mantle cell lymphoma (MCL), 9 (21%); chronic lymphocytic leukemia, 4 (10%); acute precursor B-cell lymphoblastic leukemia/lymphoma, 2 (5%); and other low-grade B-cell lymphomas, 3 (7%). All MCLs had overexpression of bcl-1 or the t(11;14) and were CD43+. All FLs had typical histomorphologic features and were bcl-2+ and bcl-6+ but CD43-. Of 14 LBCLs, 5 were histologically high-grade. Six (43%) of 14 patients with LBCL died within 10 months of diagnosis of CD5+CD10+ lymphoma (median survival, 4 months), including all 3 patients with stage IV disease and 2 of 5 with histologically high-grade lymphoma. Our findings indicate that coexpression of CD5 and CD10 is rare but occurs in diverse subtypes of B-cell lymphoma. Investigation of bcl-1, bcl-6, and CD43 and morphologic evaluation may resolve the potential confusion in diagnosis and lead to the recognition of the correct lymphoma subtype.

Adult↗

An unusual case of leukemic mantle cell lymphoma with a blastoid component showing loss of CD5 and aberrant expression of CD10.

Characteristically, mantle cell lymphoma (MCL) expresses surface immunoglobulin (sIg), CD19, CD20, and CD5 and lacks CD10 and CD23. Rare CD5-MCL variants have been described. This report describes a case of leukemic MCL with morphologically and immunophenotypically distinct classic MCL and blastoid-variant MCL (BV-MCL) components. The classic MCL had typical morphologic features and immunophenotype (kappa sIg light chain-restricted and CD5+; CD10- and CD23-). The BV-MCL had larger nuclei and open chromatin; these cells also were kappa sIg light chain-restricted; however, they were CD10+ and CD5-. Fluorescence in situ hybridization studies demonstrated cyclin D1-immunoglobulin heavy chain gene fusion in both components; the bone marrow biopsy cellularity was replaced by CD10+ and cyclin D1+ and CD5-BV-MCL. This case illustrates the phenotypic heterogeneity of MCL and underscores the need for histopathologic correlation and, in some instances, ancillary genetic studies to accurately classify B-cell lymphomas.

Bone Marrow Cells↗

The ectopeptidases CD10, CD13, CD26, and CD143 are upregulated in gastric cancer.

Due to their extracellular orientation, the ectopeptidases CD10, CD13, CD26, and CD143 have numerous functions, including the post-secretory processing of the neuropeptides and peptide hormones involved in the regulation of growth and differentiation in the gastrointestinal tract. We investigated the transcription and expression pattern of these four ectopeptidases in gastric carcinomas (GC), the corresponding non-neoplastic epithelium, a selection of lymph node metastases (LNM), and the MKN28, AGS, NCI-N87, KATO III gastric cancer cell lines. The gastric foveolar epithelium did not express CD10, CD13, or CD143, but the intestinal metaplasia demonstrated strong immunoreactivity at the brush border for all four ectopeptidases. CD10, CD13, and CD143 were significantly up-regulated in GCs and the lymph node metastases, confirming that they are important for the tumor cell biology. However, there is a lack of correlation between expression in intestinal metaplasia and tumor, as well as in tumor and LNM. Cell proliferation assays were performed with MKN28 and AGS, in which inhibition of CD10 significantly reduced the growth of both cell lines, and inhibition of CD13 significantly increased the proliferation of the AGS cells, indicating that the ability to degrade gastrointestinal peptides may play an important role in the pathobiology of gastric cancer.

Adult↗

Infusion of anti-CD10 monoclonal antibody (J5) following ablative chemotherapy in a patient with refractory pre-B acute lymphoblastic leukemia.

The case of a 9-year old girl with end-stage refractory pre-B CD10/CALLA positive acute lymphoblastic leukaemia is described. The patient was treated with high doses of cytarabine followed by intravenous anti-CD10 monoclonal antibody (J5) in an effort to prevent the recovery of the leukemic CD10 positive clone following the bone marrow hypoplasia resulting from the chemotherapy. The number of CD10 positive cells dissapeared both in the peripheral blood as well as in the bone marrow, but when granulocytic recovery ensued, the patient died from respiratory infection. No evidence of antigenic modulation of the CD10 antigen was observed in the blast cells.

Antibodies, Monoclonal↗

Modulation of CALLA (CD10) antigen on cultured ALL (REH) cells: effect of various modulators.

Phorbol ester (TPA)-induced down-regulation of the common ALL (CALLA) antigen was studied by continuous flow immunocytometry with the aid of several CD10 monoclonal antibodies, including a new CD10 monoclonal antibody (DGH-10-1-A9), shown to be of IgG1 isotype, recognizing a 100 kDa cell surface protein and effectively inhibited by a series of reference CD10 monoclonal antibodies. The TPA-induced down-regulation of CALLA on REH cells was demonstrated with the aid of the following CD10 monoclonal antibodies: J-5, VIL-A1 and DGH-10-1-A9. No major modulations in cell surface expression of CALLA on REH cells were observed after induction with 1,25-(OH)2 vitamin D3, retinoic acid, recombinant interferon (IFN) alpha 2a and recombinant interleukin 2.

Antibodies, Monoclonal↗

CD10+ stromal cells form B-lymphocyte maturation niches in the human bone marrow.

In adult mammals, early B-lymphopoiesis takes place in the bone marrow in close association with stromal cells. Both the phenotype of the stromal cells and the molecules involved in this essential interaction are as yet inadequately described. In this study, all benign, differentiating B-cells (Pax-5+ lymphoid cells) are shown, by using two-colour immunohistochemistry on biopsies from human bone marrow, to be in close contact with scant dendritic CD10+ stromal cells until they leave via the sinusoids. This CD10+ stromal cell population does not fully overlap with the VCAM-1+ stromal cell population. Furthermore, using a set of B-cell differentiation markers (TdT, Pax-5, and CD20), B-cell development is shown to be spatially oriented, with maturation progressing towards bone marrow sinusoids. In conclusion, CD10+ stromal cells form distinct B-lymphocyte maturation niches in the human bone marrow.

B-Lymphocytes↗

The increase of low density subpopulations and CD10 (CALLA) negative neutrophils in severely infected patients.

We investigated the changes in polymorphonuclear leukocyte (PMN) subpopulations that accompany severe bacterial infection and examined their usefulness as a parameter for assessing the severity of infection. The Percoll density gradient was used to fractionate neutrophils into subpopulations of high density (1.09-1.10), intermediate density (1.08-1.09), and low density (1.07-1.08) with the majority of neutrophils from normal volunteers being of high density. By contrast, neutrophils from infected patients were of intermediate or low density, while those from severely infected patients showed a high percentage of the low density fraction with functional changes in lower chemotactic and beta-gulcuronidase activity. When each density subpopulation in the normal blood neutrophils was tested, low density PMNs had the lowest chemotaxis and minimal beta-glucuronidase activity. These results indicate that the increase in low density PMNs in patients with severe infection clearly reflects the functional impairment of PMNs. Flow cytometric analysis demonstrated that the neutrophils from severely infected patients had an decrease in CD10 expression. The percentage of CD10 positive PMNs correlated well with the severity of infection and with the clinical course of the patients. Thus, we conclude that PMN-density and CD10 expression change during severe bacterial infection, and that the measurement of PMN-subpopulations may be used to complement the clinical assessment of the severity of infections.

Bacterial Infections↗

Expression of CD10 on lymphoid cells associated with thymoma.

BACKGROUND: The thymoma is a mixture, in varying proportions, of epithelial and lymphoid cells. The aim of this study was to detect immature T-lineage components of lymphoid cells infiltrating thymoma tissue. METHODS: Tissue-infiltrating lymphoid cells (N = 10) and normal thymocytes (TC, N = 3) were retrieved from surgical specimens. The surface antigens of these lymphocytes were examined with flow cytometry. RESULTS: CD3 was detected on 48 +/- 19% of tissue-infiltrating lymphoid cells and 66 +/- 16% of TC, while CD19 was expressed on neither. CD4 and CD8 were co-expressed on 70 +/- 21% of Tissue-infiltrating lymphoid cells and 68 +/- 28% of TC. CD10 was expressed on 22 +/- 10% of tissue-infiltrating lymphoid cells, but was not expressed on TC (5 +/- 3%, p = 0.0003). Two-color analysis showed that the CD10+ fraction was weakly stained with CD3. It was also stained with anti-CD38 and anti-CD4, but not with anti-CD34. CONCLUSIONS: Tissue-infiltrating lymphoid cells included CD10-positive T-lineage cells. This fraction corresponds to very immature thymocyte subsets. These observations suggest that the epithelial component of a thymoma either inhibits the normal differentiation of T-lineage cells, or attracts immature T-lineage cells of bone-marrow origin.

Adult↗

Expression of aquaporins and PAX-2 compared to CD10 and cytokeratin 7 in renal neoplasms: a tissue microarray study.

Diagnostic use of antibodies against aquaporin water channel proteins and PAX-2, a nuclear transcription factor in renal development, was tested in 202 renal neoplasms, using tissue microarray technique. Immunohistochemistry for aquaporin-1, aquaporin-2, PAX-2, CD10, and cytokeratin 7 was performed on 102 clear cell renal cell carcinomas, 44 papillary renal cell carcinomas (among them 34 type 1 and 10 type 2), 24 chromophobe renal cell carcinomas, three collecting duct carcinomas (carcinomas of the collecting ducts of Bellini), and 29 oncocytomas. Aquaporin-1 expression was found in clear cell renal cell carcinomas and papillary renal cell carcinomas of both types (78 and 73%, respectively), but not in chromophobe renal cell carcinomas, collecting duct carcinomas, and oncocytomas. Aquaporin-2 expression was not seen in any of the tested tumors. PAX-2 and CD10 was found in the majority of clear cell renal cell carcinomas (88 and 85%, respectively) but only in few papillary renal cell carcinomas, chromophobe renal cell carcinomas and oncocytomas. Decrease or loss of aquaporin-1 and PAX-2 was shown in higher grades compared to lower grades of clear cell renal cell carcinomas (P<0.0001 and <0.0245, respectively). Cytokeratin 7 was rarely seen in clear cell renal cell carcinomas, type 2 papillary renal cell carcinomas, and oncocytomas, but was found in the majority of type 1 papillary renal cell carcinomas (97.1%) and chromophobe renal cell carcinomas (88%). Aquaporin-1 and PAX-2 expression was found to correlate with nuclear grading for clear cell renal cell carcinomas but not for papillary renal cell carcinomas. No correlation of tumor stage and aquaporin-1 and PAX-2 expression was seen. Aquaporin-1 and PAX-2 are reliable markers for clear cell renal cell carcinomas of lower grades but not for higher grades. CD10 expression remains stable, independent of nuclear grading.

Adenocarcinoma, Clear Cell↗

Flow cytometric detection of CD10 (cALLA) on peripheral blood B lymphocytes of neonates.

CD10 (cALLA) was detected on the surface of CD19-positive circulating lymphocytes in the peripheral blood of 32/50 neonates tested. These cells are presumed to represent immature B cells, commonly referred to as haematogones, previously undescribed in peripheral blood. The CD10+/CD19+ cells expressed lower levels of CD22 consistent with these cells being immature B lymphocytes. The presence of CD10+/CD19+ cells in the blood was not significantly correlated with a leucoerythroblastic picture, adjusted gestational age, or the presence in blood smears of medium-to-large lymphocytes with an immature appearance that morphologically resembled classic bone-marrow haematogones.

Antigens, CD↗

PMA and doxorubicin decrease viability, MTT activity and expression of CD10 marker on NALM-1 leukemic cells.

PMA (10, 20 ng/ml) and doxorubicin (5-20 ng/ml) decreased the viability and MTT-activity of NALM-1 pre-B leukemic cells (3 days' treatment). Further, CD10 was downregulated, suggesting that PMA and doxorubicin induced differentiation of NALM-1 cells. However, PMA did not alter expression of B cell markers CD20 and of mIgM. In contrast to PMA, another differentiation agent ATRA did not alter CD10 expression on NALM-1 cells but affected viability after 6 days (5, 10 ng/ml). The data in this study are the first evidence that PMA and doxorubicin inhibited viability and MTT activity and induced partial differentiation, by decreasing CD10 on NALM-1 cells.

Antibiotics, Antineoplastic↗

CD10 is expressed on human thymic epithelial cell lines and modulates thymopentin-induced cell proliferation.

Thymic hormones such as thymopoietin (TP) have been shown to regulate thymocyte differentiation and lymphocyte activation. However, it is not known whether thymopoietin affects thymic epithelial cell (TEC) functions. In this study we have examined the effect of a five amino acid active peptide (TP5), corresponding to amino acids 32-36 of TP, on the proliferation of nontransformed clones of human TEC. Our results indicate that TP5 induced reinitiation of DNA synthesis and potentiated fetal calf serum (FCS)-induced cell growth in postnatal and fetal-derived human TEC. We also found that TEC lines express high levels of endopeptidase 24.11, a cell-surface metallopeptidase also known as the CD10 antigen. We show that TP5 is cleaved by CD10 at the surface of TEC lines, indicating that this endopeptidase may regulate TP5-induced TEC proliferation. Phosphoramidon, a specific endopeptidase 24.11 inhibitor, consistently acts in synergy with TP5 to enhance FCS-induced TEC growth. Hence, we conclude that 1) TP5 alone or in combination with FCS supports the growth of TEC lines, and 2) TEC lines express high levels of CD10, which regulates TP5-induced TEC proliferation by acting as a thymic peptide degrading enzyme.

Antigens, CD↗

Expression of bcl-6 and CD10 in primary mediastinal large B-cell lymphoma: evidence for derivation from germinal center B cells?

Primary mediastinal large B-cell lymphomas (LBCLs) constitute a unique subtype of diffuse LBCLs, with distinct clinical, immunophenotypic, and morphologic features. These lymphomas are thought to originate from the thymus, and it has been hypothesized that they derive from a population of B lymphocytes normally present in the thymic medulla. Most diffuse LBCLs harbor somatic mutations in their immunoglobulin genes, suggesting that they have been exposed to the germinal center. To investigate the possible relationship of mediastinal LBCLs to germinal center B cells, we analyzed the expression of bcl-6 and CD10 in 19 mediastinal LBCLs, using an immunoperoxidase technique on formalin-fixed tissue. We found that 19 of 19 (100%) mediastinal LBCLs were bcl-6+ and 6 of 19 (32%) mediastinal LBCLs were CD10+. Because mediastinal LBCLs usually lack BCL-6 gene rearrangement or mutations, expression of bcl-6 and CD10 in these tumors tends to support a germinal center derivation.

Adolescent↗

Mesonephric adenocarcinoma of the uterine corpus: CD10 expression as evidence of mesonephric differentiation.

Mesonephric (wolffian) neoplasms of the female genital tract are infrequent and found in sites where embryonic remnants of wolffian origin are usually detected, such as the uterine cervix, broad ligament, mesosalpinx, and ovary. Their diagnosis is difficult because of the absence of specific immunohistochemical markers for mesonephric derivatives. We present the first report of adenocarcinoma of mesonephric type arising as a purely myometrial mass without endometrial or cervical involvement in the uterine corpus of a 33-year-old woman. The tumor showed a combination of patterns, with retiform areas, ductal foci, and small tubules with eosinophilic secretion, which merged with solid sheets of cells with a sarcomatoid appearance. Immunohistochemically, neoplastic cells were diffusely positive for cytokeratin 7, epithelial membrane antigen, and CD15 and focally positive for BerEP4 and vimentin. A hitherto unreported feature was the positivity for CD10 in neoplastic cells, which was also present in a large number of control tissues obtained from male mesonephric derivatives and female mesonephric remnants and tumors. Furthermore, CD10 was negative in controls from müllerian epithelia of the female genital tract and in their corresponding tumors. Therefore, the expression of CD10 by mesonephric remnants may be useful in establishing the diagnosis of tumors with mesonephric differentiation.

Adenocarcinoma↗

Expression of granulocyte colony-stimulating factor receptor on CD10-positive human B-cell precursors.

We examined the expression of CD10 and G-CSF receptor (G-CSFR) on the lymphoid population of mononuclear cells obtained from bone marrow (BM) using two-colour analysis. In the BM of children with ALL in remission, the CD10+ population was significantly increased (20.6 +/- 5.1% compared with that of controls (2.5 +/- 0.5%). More than half (61.3 +/- 2.9%) of the CD10+ cells co-expressed G-CSFR, but not CD13. These results indicate G-CSFR+ B-cell precursors are markedly increased in BM of ALL in remission, suggesting the probable involvement of G-CSF in the human early B-cell ontogeny.

Adolescent↗