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CD10 expression in follicular lymphoma versus reactive follicular hyperplasia: evaluation in paraffin-embedded tissue.

The differentiation of reactive follicular hyperplasia (RFH) from follicular lymphoma (FL) may be a diagnostic challenge and require the use of adjuvant studies. Antibodies to CD10 have been used with flow cytometry and frozen tissue sections and recently have become available for use with paraffin-embedded tissue. We sought to investigate the utility of CD10 in the differentiation of RFH from FL in paraffin-embedded tissue. Twenty-three cases of FL and 19 cases of RFH were evaluated after immunostaining with antibodies to CD3, CD20, BCL2, and CD10 antigens. Intensity of CD10 expression was graded. CD10 expression was present in 87% of cases of FL. Follicles demonstrated strong positivity in 70%. One CD10-positive case of FL showed equivocal staining for BCL2 and one an absence of staining for BCL2. Weaker but definite staining was present in 17%, and 13% were negative for CD10. In contrast, none of the cases of RFH was strongly positive for CD10 expression, with 26% demonstrating weak immunostaining, one case showing equivocal staining, and 68% being entirely negative. CD3, CD20, and BCL2 stained appropriately in all cases. These findings indicate that immunohistochemical staining of paraffin-embedded tissue sections for CD10 may help differentiate reactive from neoplastic follicular lesions.

Antigens, CD20↗

Expression of the CD10 antigen (neutral endopeptidase) by mesenchymal tumors of the skin.

BACKGROUND: The CD10 (or CALLA) antigen is a neutral endopeptidase expressed by a variety of non-hemopoietic cells, including fibroblasts in various tissues. So far little or conflicting data exist concerning the expression of CD10 in normal and pathologic skin. METHODS: We investigated the immunohistochemical expression of the CD10 antigen on formalin-fixed, paraffin-embedded tissue specimens of normal skin and 162 cutaneous proliferative lesions, mostly mesenchymal tumors. RESULTS: In normal skin CD10 immunoreactivity was found in periadnexal mesenchymal cells. In skin tumors, CD10+ cells were found mainly in dermatofibromas and, to a lesser extent, in Dermatofibrosarcoma protuberans and neurofibromas. Metastatic (and to a lesser extent primary) melanomas also occasionally expressed CD10. CONCLUSION: Our results show that the CD10 antigen is expressed by mesenchymal cells of normal human dermis, presumably encompassing a subset of CD34+ dermal dendrocytes and/or periadnexal fibroblasts. The CD10 antigen could be used as an adjunct to the diagnosis of some spindle-cell cutaneous tumors such as dermatofibromas and Dermatofibrosarcoma protuberans, but its value as a single marker is rather limited. The possible role of CD10 as a progression marker in melanoma is interesting and merits further study.

Antibodies, Neoplasm↗

The induction of CD10 on a pre-B leukemia cell line occurs with progression of the disease in scid mice.

We have previously demonstrated the engraftment and dissemination of human pre-B acute lymphoblastic leukemia (ALL) cells into scid mice. In the current study, the temporal pattern of infiltration of a CD10- pre-B leukemia line (G2) in various murine tissues and the progression of the disease in the whole animal were monitored by quantifying human CD44 mRNA expression by the polymerase chain reaction (PCR). Irradiated scid mice were injected intravenously with 10(6) G2 cells and killed 3 days to 10 weeks later. After 2 weeks, leukemic cells were found mostly in bone marrow, but also in lung. At 6 to 7 weeks, spleen and lung contained 30% human RNA, while peripheral blood, liver, and kidney contained 2-3%. Infiltration to brain and thymus was observed at 8-9 weeks. In terms of the whole animal, spleen and liver were the major sites of tumor burden. The induction of CD10 expression was previously observed in transplanted CD10- G2 leukemic cells recovered from scid thymus at 10-12 weeks, which corresponds to the terminal stage of disease. In this study, the CD10 expression on the leukemic cells was monitored at earlier time points by flow cytometry and quantitative PCR. Induction of CD10 was first observed in bone marrow, spleen, peripheral blood, and liver at 6-7 weeks (10-fold), at the time of the onset of dissemination of the leukemia. Despite the presence of 30% human RNA in lung at 6-7 weeks, CD10 induction was not significant in that site before 10 weeks. Increased levels of CD10 were seen in all tissues between 8 and 10 weeks; the highest levels were observed in leukemic cells proliferating in thymus (113-fold) and in those found in circulation. These findings suggest that initial induction of CD10 occurs in hematopoietic tissues at the time of rapid proliferation of the leukemic cells and their infiltration of several tissues. At later time points, the increase in CD10 expression is seen on the leukemic cells found in all peripheral organs suggesting an association with disease progression.

Animals↗

In vivo and in vitro antitumor activity of mitomycin C conjugates at 7-N position through a linker containing thiocarbamate bond with CD10 monoclonal antibody.

Through a linker containing thiocarbomate bound to the 7-N position of mitomycin C (MMC), conjugates with a monoclonal antibody to CD10 (NL-1) were prepared, and their antitumor activities were examined. All five conjugates, except one, showed in vitro cytotoxicity to two CD10+ lymphoid cell lines superior to MMC. The conjugate displaying the highest cytotoxicity was selected and further tested against three CD10+ and two CD10- lymphoid cell lines in vitro. The conjugate with NL-1 antibody demonstrated higher cytotoxic activity against CD10+ tumor cells than the control conjugate with normal immunoglobulin, while there was no significant difference, when tested against CD10- tumors. The cytotoxic activity of the NL-1 conjugate to CD10+ tumors was significantly blocked by NL-1 antibody. In vivo antitumor activity of the NL-1 conjugate was then tested against a CD10+ tumor transplanted to nude mice, and side effects were recorded. The NL-1 conjugate (4 mg/kg) showed an in vivo antitumor effect similar to MMC (2 mg/kg), which is at nearly maximal tolerable dose; the latter induced decreases in numbers of leukocytes and platelets, while the former did not, suggesting less side effect by the NL-1 conjugate. Since MMC demonstrates a broad spectrum of antitumor activity, the conjugate, as such, may be applicable for the treatment of cancer patients.

Animals↗

CD10 expression in diffuse large B-cell lymphomas does not influence survival.

CD10 expression is considered as a marker of centrofollicular-derived diffuse large B-cell lymphomas (DLBCL). The aim of our study was to determine retrospectively among 98 patients with DLBCL, enrolled in the LNH93 trial of the Groupe d'Etude des Lymphomes de l'Adulte (GELA) and homogeneously treated with high-dose cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-like regimen [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisone (ACVBP)], the expression of CD10 using immunohistochemistry and its correlation with morphological features and clinical parameters. Of the 98 patients studied, 33 (34%) expressed CD10. There was no correlation among clinical parameters, International Prognostic Index risk groups and CD10 expression, with the exception of lactic dehydrogenase levels, which were lower in CD10-negative cases (P=0.005). There was no significant correlation between CD10 expression and morphological subtyping of DLBCL. Indeed, centrofollicular-derived DLBCL may present with numerous immunoblasts or as an immunoblastic lymphoma. Overall survival rate and event-free survival were not significantly different according to CD10 expression (P=0.44 and P=0.34 respectively). Therefore, it appears that CD10 expression does not influence survival or event-free survival in DLBCL.

Biomarkers, Tumor↗

CD10 is a sensitive and diagnostically useful immunohistochemical marker of normal endometrial stroma and of endometrial stromal neoplasms.

AIMS: The CD10 antigen is expressed in acute lymphoblastic leukaemia and follicle centre cell lymphoma. A recent study investigating the expression of CD10 in a wide range of non-haematopoietic neoplasms found positive staining in a small number of endometrial stromal sarcomas as well as in normal endometrial stroma. The present study aimed to ascertain whether CD10 positivity is indeed found in normal endometrial stroma and endometrial stromal neoplasms. Staining of a range of tumours which can be confused morphologically with endometrial stromal neoplasms was also undertaken to ascertain whether antibodies against CD10 are of value in a diagnostic sense. METHODS AND RESULTS: Neoplasms included in the study were endometrial stromal nodule (n=1), low-grade endometrial stromal sarcoma (ESS) (n=13), high-grade ESS (n=6), mixed endometrial stromal-smooth muscle tumour (n=1), uterine cellular leiomyoma (n=10), uterine leiomyosarcoma (n=5), adult granulosa cell tumour (AGCT) (n=10), undifferentiated endometrial carcinoma (n=6), uterine carcinosarcoma with an endometrial stromal component (n=1) and type II uterine mesenchymal tumour with sex cord-like elements (n=1). Cases of proliferative (n=5), secretory (n=5) and atrophic (n=3) endometrium were also stained. There was positive staining of stroma but not of glands in all cases of non-tumorous endometrium. There was positive staining of the endometrial stromal nodule and of all low-grade ESS. Staining in these varied but was often diffuse and of moderate to strong intensity. There was positive staining of four of six high-grade ESS, but this was usually focal. There was also positive staining of the endometrial stromal component in the mixed endometrial stromal-smooth muscle tumour and in the uterine carcinosarcoma. Most cellular leiomyomas were completely negative although three exhibited weak positivity. There was some positivity, usually focal or weak, of three of five leiomyosarcomas. Most AGCT and undifferentiated carcinomas were completely negative although one case of each exhibited focal staining. There was focal staining of the type II uterine mesenchymal tumour with sex cord-like elements. CONCLUSION: CD10 is a reliable and sensitive immunohistochemical marker of normal endometrial stroma. Positivity, which is often strong and/or diffuse is found in endometrial stromal nodules and low-grade ESS. Positive staining with CD10, when strong and diffuse, may be useful in distinguishing these tumours from histological mimics, especially cellular leiomyoma and AGCT which are generally negative. In this situation, CD10 should be used as part of a panel which might include desmin and alpha-inhibin depending on the differential diagnosis considered. Positive staining with CD10 in a high-grade uterine sarcoma which is negative with muscle markers might indicate endometrial stromal differentiation and identify a group of neoplasms which it is correct to diagnose as high-grade ESS rather than undifferentiated uterine sarcoma.

Endometrial Neoplasms↗

Cutaneous b-cell lymphomas of follicular and marginal zone types: use of Bcl-6, CD10, Bcl-2, and CD21 in differential diagnosis and classification.

Cutaneous follicular lymphomas (FLs) and cutaneous B-cell lymphomas of extranodal marginal zone (MZL)/mucosal-associated lymphoid tissue (MALT) type may have morphologic overlap, despite the fact that they are thought to be of distinct derivation (germinal center vs. postgerminal center). The problem is compounded by the reported absence of bcl-2 expression by many cutaneous FLs, leading to speculation that cutaneous FL may be unrelated to nodal FL. The authors analyzed the expression of the germinal center-associated antigens bcl-6 and CD10 and of bcl-2 in 18 cutaneous B-cell lymphomas (10 FLs and eight MZLs), in relationship to CD21+ follicular structures, to clarify the relationship of nodal to cutaneous FLs and to explore the value of these antigens in differential diagnosis. The authors studied 10 cutaneous FLs (seven primary and three secondary) and eight MZLs (six primary and two secondary). The FLs (found in six men and four women age 45-75 years) involved the trunk (n = 3) and scalp, face and neck (n = 7). The MZLs (found in five women and three men age 34-81 years) involved the trunk (n = 4), face and neck (n = 2), and arm (n = 2). Immunostaining for CD21, bcl-6, CD10, and bcl-2 allowed the delineation of compartments within the tumors and yielded distinct patterns of staining in FL and MZL. In both follicular and interfollicular/diffuse areas of FL the neoplastic cells were bcl-6+ (10 of 10), often CD10+ (seven of 10, four of seven primary), and bcl-2+ (nine of 10, six of seven primary). Only three of seven cases (one of five primary) had bcl-2 rearrangement detectable by polymerase chain reaction. In the MZLs, the neoplastic B-cells were bcl-6-, CD10-, and bcl-2+ (eight of eight). Three patterns of CD21+ follicles were identified in MZL: reactive germinal centers, uniformly bcl-6+, CD10+, and bcl-2- (five of eight MZLs); colonized follicles, both bcl-6-, bcl-2+, and L26+ cells, and bcl-6+ and bcl-2- cells (five of eight MZLs); and expanded/colonized follicular dendritic cell meshworks, bcl-6- and bcl-2+ B cells with rare residual bcl-6+ and bcl-2- cells (four of eight MZLs). The authors conclude that cutaneous FLs express bcl-6 uniformly, usually express CD10 and bcl-2, and have a follicular pattern similar to nodal FL and consistent with a germinal center origin. The immunophenotype of cutaneous FL is distinct from that of cutaneous MZL, which is negative for bcl-6 and CD10. Colonized follicles in MZL, identified by CD21+ follicular dendritic cell meshworks, contained numerous bcl-6- and bcl-2+ B cells, and were readily distinguished from neoplastic follicles in FL. Conversely, CD21- interfollicular and diffuse areas in FLs contained bcl-6+ and CD10+ cells, which were not seen in diffuse areas of MZLs. Thus, the combination of bcl-2, bcl-6, and CD21 staining is useful for the distinction of cutaneous MZL from cutaneous FL.

Adult↗

Comparison of genetic aberrations in CD10+ diffused large B-cell lymphoma and follicular lymphoma by comparative genomic hybridization and tissue-fluorescence in situ hybridization.

CD10 is one of the hallmarks of germinal center B-cells where follicular lymphomas (FL) originate. It has not been clearly established, however, whether CD10(+) diffuse B-cell lymphomas (DLBCL) are genetically similar to FL. We therefore examined 19 CD10(+) DLBCL and 40 FL by means of comparative genomic hybridization (CGH) and tissue-fluorescence in situ hybridization (T-FISH). Chromosomal imbalance was more frequently detected in CD10(+) DLBCLs (19/19) than in FLs (24/40). Significant differences were found in eight frequently imbalanced regions, namely those with gains of chromosomes 7q and 12 and those with losses of chromosomes 1p, 4p, 6q, 15q, 16p and 17. Amplification of the 3q region where BCL6 is located is reported to occur frequently in DLBCL, but it was only found in one of the 19 CD10(+) DLBCL cases we examined. The involvement of t(14;18) in CD10(+)+ DLBCL (31%) and in FL (73%) was significantly different (P = 0.0064). The CGH pattern of CD10(+) DLBCL with t(14;18) was also different from that of FL with t(14;18). Taken together, our results indicate that CD10(+) DLBCL constitutes a unique subtype entity with genetic characteristics significantly different from those of FL and DLBCL.

Aged↗

Bcl-2, Bcl-6 and CD10 expression in cutaneous B-cell lymphoma: further support for a follicle centre cell origin and differential diagnostic significance.

BACKGROUND: Primary cutaneous follicle centre cell lymphomas (PCFCCLs) are the most common type of cutaneous B-cell lymphoma. There is ongoing discussion on the origin of the neoplastic B cells in these PCFCCLs, and consequently on their relation to the groups of primary cutaneous marginal zone B-cell lymphomas (PCMZLs) and nodal follicular lymphomas. OBJECTIVES: To define better the neoplastic B cells in PCFCCLs, and to find out if differences in the expression of the antiapoptopic protein Bcl-2, and Bcl-6 and CD10, molecules which are normally expressed by the neoplastic B cells in nodal follicular lymphomas, might have diagnostic or prognostic significance in cutaneous B-cell lymphoproliferative disorders. METHODS: Pretreatment biopsies of well-defined groups of PCFCCL (n = 24), PCMZL (n = 14), primary cutaneous large B-cell lymphoma of the leg (PCLBCL-leg; n = 19), secondary cutaneous follicular lymphoma (n = 3) and cutaneous pseudo-B-cell lymphoma (n = 6) were investigated by immunohistochemistry for expression of Bcl-2, Bcl-6 and CD10. RESULTS: The PCFCCLs consistently expressed Bcl-6, whereas CD10 and Bcl-2 were expressed in only one and two of 24 cases, respectively. In contrast, PCMZLs were always negative for Bcl-6 and CD10, but were Bcl-2 positive, whereas skin and lymph node localizations of secondary cutaneous follicular lymphomas consistently expressed all of Bcl-2, Bcl-6 and CD10. Reactive follicle centre cells in pseudo-B-cell lymphomas expressed Bcl-6 (six of six cases) and CD10 (five of six cases), but not Bcl-2. PCLBCL-leg was Bcl-6 positive and CD10 negative in all cases, irrespective of clinical outcome, and strongly expressed Bcl-2 protein in all but two cases. CONCLUSIONS: The results of the present study provide further support for the follicle centre cell origin of both PCFCCL and PCLBCL-leg, and indicate that staining for Bcl-2, Bcl-6 and CD10 can serve as an important adjunct in the differential diagnosis of cutaneous B-cell lymphoproliferative disorders.

DNA-Binding Proteins↗

The diagnostic utility of MOC31, BerEP4, RCC marker and CD10 in the classification of renal cell carcinoma and renal oncocytoma: an immunohistochemical analysis of 328 cases.

AIMS: To demonstrate the diagnostic utility of MOC31, BerEP4, renal cell carcinoma marker (RCC Ma) and CD10 in the classification of RCC and renal oncocytoma, based upon a comprehensive immunohistochemical analysis. METHODS AND RESULTS: Immunohistochemistry was performed on 328 samples consisting of 256 clear cell/conventional, 27 papillary, 28 chromophobe, five collecting duct, five unclassified RCCs and seven renal oncocytomas using antibodies MOC31, BerEP4 and antibodies against cytokeratins (KL-1, CAM5.2, 34betaE12, cytokeratin 7), RCC Ma, epithelial membrane antigen, E-cadherin, CD10, CD15 and vimentin. Multivariate analysis showed that MOC31, BerEP4, RCC Ma and CD10 have discriminatory value. MOC31 and BerEP4 chiefly labelled distal tubules of normal kidney while RCC Ma and CD10 labelled the proximal tubules. Twenty-three chromophobe RCCs (82%) were reactive for MOC31, while only four clear cell RCCs and three papillary RCCs were positive for this marker. Clear cell RCCs were characterized by a high positive rate for CD10 (82%) and a low positive rate for BerEP4 (27%). Papillary RCCs frequently coexpressed RCC Ma and BerEP4 (51%). All renal oncocytomas were negative for MOC31 and CD10. CONCLUSIONS: MOC31 has diagnostic merit in discerning chromophobe RCC. The CD10+/BerEP4- profile and RCC Ma+/BerEP4+ profile achieve moderate sensitivity and good specificity for clear cell RCC and papillary RCC, respectively. The non-reactivity for both MOC31 and CD10 is helpful in distinguishing renal oncocytoma from RCC. When properly selected, antibodies have immunohistochemical diagnostic utility for the classification of renal cortical epithelial tumours.

Adenoma, Oxyphilic↗

Regeneration of CALLA (CD10+), TdT+ and double-positive cells in the bone marrow and blood after autologous bone marrow transplantation.

In this prospective study we investigated the frequency of CD10+, TdT+ and CD10+TdT+ mononuclear cells in the bone marrow (BM) and peripheral blood (PB) before and after autologous bone marrow transplantation (ABMT). 49 patients treated for acute lymphoblastic or myeloblastic leukaemia, malignant lymphoma or multiple myeloma were included. A significant increase in CD10+ cells occurred in BM in both children and adults after ABMT. In children, we also found a significant increase in CD10+ cells in PB. In individual patients remaining in remission, up to 34% CD10+ cells having a normal Ig kappa/lambda light chain ratio were recorded after ABMT. In children, the percentage of TdT+ and CD10+ TdT+ cells increased significantly in BM. In most cases the CD10/TdT-ratio was greater than 1.0, but during early regeneration after ABMT this ratio was less than 1.0 in several patients remaining in complete remission. In patients remaining in remission, CD10+TdT+ cells were detected in the blood in only 2 out of 140 samples tested, and the proportion of these cells never exceeded 0.03%. We conclude that quantitation of CD10+TdT+ cells in peripheral blood is helpful in the evaluation of complete remission in patients treated for pre-B-ALL.

Adult↗

CD10 expression in stromal cells of oral cavity squamous cell carcinoma: a clinic and pathologic correlation.

OBJECTIVE: CD10 is expressed on the majority of follicle-center lymphomas and Burkitt lymphomas. CD10 has also been shown to be present in a variety of other neoplasms. DESIGN: The aim of this study was a correlation of CD10 and several parameters: age, tumor size, presence of lymph node metastases, clinic stage, histologic grading, presence of local recurrences. MATERIALS AND METHODS: The tissues of 77 consecutive patients with oral cavity squamous cell carcinoma were evaluated using immunostaining with monoclonal antibody for CD10. MAIN OUTCOME MEASURES: Highly significant correlations were found with the lymph node status, the presence of local recurrences and the histologic grading. The presence of CD10-positive cells was not correlated with the age of patients, tumor size and clinic stage. RESULTS: The results of the present study show that in oral squamous cell carcinoma CD10 positivity is an indicator of worse prognosis. Another strong correlation was found with the presence of local recurrences. Also the histologic grade was significantly correlated with the CD10 positivity. CONCLUSION: Our results point to the fact that CD10 expression can, perhaps, have an important role in tumor invasion, probably facilitating the occurrence of metastases.

Adult↗

CD10 expression in non-small cell lung cancer.

CD10 is a cell surface endopeptidase that inactivates various potentially growth stimulatory peptides. In lung cancer cell lines this downregulation has been associated with increased proliferation. Downregulation of CD10 in lung cancer tissue is described, suggesting a potential role in carcinogenesis and a possible use of CD10 as a prognostic marker. We aimed to determine the rate of CD10 expression in our non-small cell lung cancer (NSCLC) collection and to clarify its correlation with clinicopathological parameters and patient survival. 114 NSCLC were analysed immunohistochemically using a monoclonal CD10 antibody (clone NCL-CD10-270) on an NSCLC tissue micro array. The staining was semiquantitatively scored. CD10 expression was observed in 19% of cases, without any significant association with tumour type, -size, -grading, nodal status, clinical stage, and patient survival time. We conclude that a diagnostic use of CD10 immunostaining in NSCLC is unlikely.

Adenocarcinoma↗

CD10-MUM1+ follicular lymphoma lacks BCL2 gene translocation and shows characteristic biologic and clinical features.

CD10 and MUM1 are representative B cell differentiation markers. Follicular lymphoma (FL) is usually positive for CD10 and negative for MUM1. In this study, however, we compared 22 FLs with peculiar phenotype CD10-MUM1+ with 119 typical CD10+MUM1- FLs. All CD10-MUM1+ FL patients exhibited follicular structure with follicular dendritic meshwork, and a high rate of somatic hypermutation and ongoing mutation, similar to typical FL. However, CD10-MUM1+ FLs were encountered frequently in the elderly compared with CD10+MUM1- typical FLs (67.0 versus 58.7 years, P < .01), showed high grade (grade 3A or 3B) morphology (91% versus 17%, P < .001), diffuse proliferation (59% vs 19%, P < .001), and lacked BCL2/IGH translocation (5% versus 92.5%, P < .001), which is the most characteristic aberration in FL, and 88% showed BCL6 gene abnormalities (translocation or amplification). Our results indicate that CD10-MUM1+ FL is different from typical FL with respect to biologic and clinical features.

Aged↗

Decreased CD10 expression in grade III and in interfollicular infiltrates of follicular lymphomas.

CD10 expression in various grades and interfollicular infiltrates of follicular lymphoma (FL) has not been well documented. Immunohistochemical staining for CD10 (clone 56C6) was performed on paraffin-embedded tissue from 26 cases of classic FL. Negative or weak expression of CD10 was more frequent in grade III (5/6 [83%]) than in grade I FLs (3/15 [20%]). CD10+ interfollicular infiltrates were present in 16 cases. Six (38%) of 16 cases showed that CD10 expression was strong or moderate in follicular areas but weak or negative in interfollicular infiltrates. Our results suggest that CD10 expression is frequently weak to negative in grade III and in interfollicular infiltrates of FLs. Therefore, lack of CD10 expression on small specimens, such as from needle core biopsy or fine-needle aspiration, does not preclude the possibility of a diagnosis of FL. Furthermore, lack of CD10 expression in diffuse large B-cell lymphoma does not exclude the possibility that the neoplastic lymphocytes are of follicle center cell origin.

Adult↗

Human cytomegalovirus infection downregulates expression of the cellular aminopeptidases CD10 and CD13.

During the course of a productive infection, human cytomegalovirus (HCMV) has a sophisticated relationship with its host cell. An increasing number of virus-encoded genes are being identified which act specifically to usurp or modulate functions in the host cell associated with transcriptional control, cell signalling, and protein synthesis. While HCMV infection is associated with a general upregulation of cellular gene expression, the expression a small subset of cellular proteins, including the MHC-1 heavy chain and fibronectin, is downregulated. This study now identifies two additional cellular proteins, aminopeptidase N (CD13) and neutral endopeptidase (CD10), that are downregulated during HCMV infection. While aminopeptidase N and neutral endopeptidase exhibit no significant sequence homology, both are expressed on the cell surface and have very similar enzymatic properties. HCMV infection was associated with reduced surface expression and enzyme activity of CD13 and CD10, an apparent decrease in the rate of synthesis of both proteins in metabolic-labelling experiments, and inhibited glycosylation of the nascent CD13 and CD10 polypeptide chains that were synthesized. Levels of CD10 poly A+ RNA were suppressed efficiently at all stages of virus infection; however, the reduction in CD13 poly A+ RNA levels was much less pronounced. This differential effect suggests that HCMV may be downregulating expression of CD10 and CD13 by independent mechanisms. Indeed, treatment of cells with an inhibitor of viral DNA synthesis blocks downregulation of CD13, whilst downregulation of CD10 is unaffected. While it is not yet clear what advantage is bestowed on the virus by downregulating expression of CD13 and CD10, aminopeptidases are known to have a role in peptide processing in both the MHC class I the MHC class II antigen presentation pathways.

CD13 Antigens↗

[Expression of CD10 and renal cell carcinoma marker in clear cell renal cell carcinoma: analysis on tissue arrays].

OBJECTIVES: CD10 and renal cell carcinoma (RCC) marker antibodies react against proteins of the epithelium of the renal proximal tubule, being expressed by renal cell carcinomas. The frequence and pattern of expression of both markers are analysed in a series of clear cell renal cell carcinomas. METHOD: Two tissue arrays were used, which were composed of cylinders obtained with a 16G needle from 40 paraffin blocks that corresponded to clear cell renal cell carcinomas. The labeled streptavidin-biotin technique was performed (LSAB2, Dako) using CD10 and RCC monoclonal antibodies (Novocastra), testing different antigen retrieval methods for RCC. Immunoreactivity was evaluated as + (isolated cells or focal staining); ++ (moderate) and +++ (extense). RESULTS: Thirty cases (75%) were positive for CD10: 12 +; 5 ++ and 13 +++. The best antigen retrieval method for RCC was a double enzyme digestion (trypsin + protease). Twenty cases (50%) were positive for RCC: 7 +; 5 ++ and 8 +++. Four cases out of the 20 immunoreactive for RCC were negative for CD10. The 16 remaining cases also expressed CD10. CONCLUSIONS: CD10 and RCC are often expressed by clear cell renal cell carcinomas, and they may be useful markers to suggest a renal origin of carcinomas. RCC is less sensitive than CD10. Staining for both of them is usually focal, and thus sensitivity of these techniques decreases when small samples are investigated, such as tissue arrays. The antigen retrieval method is essential for RCC immunohistochemical detection, obtaining the best results with the use of proteolytic enzymes.

Biomarkers, Tumor↗

CD10 is expressed in a subset of chromophobe renal cell carcinomas.

CD10 has been considered a useful marker in the diagnosis of renal carcinomas, because of its expression in clear cell and papillary renal cell carcinomas and its absence in chromophobe renal cell carcinomas. On the other hand, chromophobe renal cell carcinoma expresses parvalbumin, which is absent in clear cell and papillary renal cell carcinomas. To further address the relevance of these markers, we studied the expression of CD10 and parvalbumin in 42 samples of chromophobe renal cell carcinoma (seven of which had aggressive features, including invasion beyond the renal capsule, renal vein invasion, metastases, or sarcomatoid transformation), 75 clear cell renal cell carcinomas (eight metastatic) and 51 papillary renal cell carcinomas (two metastatic). CD10 was found in 100% of clear cell renal cell carcinomas, 63% of papillary renal cell carcinomas and in all metastatic cases of both types. At variance with previous studies, we found CD10 expression in from 30 to 90% of the neoplastic cells, in 11 of 42 (26%) chromophobe renal cell carcinomas. The CD10-positive cases included five of the seven (71%) chromophobe renal cell carcinoma with aggressive features. Statistical analysis showed significant association of CD10-positive tumors with clinicopathologic aggressiveness (P=0.003) and mitotic figures (P=0.04). Parvalbumin was strongly expressed in all primary and metastatic chromophobe renal cell carcinomas. Western blot analysis was utilized to confirm the expression of both CD10 and parvalbumin in chromophobe renal cell carcinomas.

Adenocarcinoma, Clear Cell↗