View source for Neprilysin

{{Infobox_gene}}

'''Neprilysin''' ({{IPAc-en|ˌ|n|ɛ|p|r|ᵻ|ˈ|l|aɪ|s|ᵻ|n}}), also known as '''membrane metallo-endopeptidase''' ('''MME'''), '''neutral endopeptidase''' ('''NEP'''), '''cluster of differentiation 10''' ('''CD10'''), and '''common acute lymphoblastic leukemia antigen''' ('''CALLA''') is an [[enzyme]] that in humans is encoded by the ''MME'' gene. Neprilysin is a [[zinc]]-dependent [[metalloprotease]] that cleaves peptides at the amino side of hydrophobic residues and inactivates several peptide hormones including [[glucagon]], [[enkephalin]]s, [[substance P]], [[neurotensin]], [[oxytocin]], and [[bradykinin]].<ref name="entrez">{{cite web | title = Entrez Gene: Membrane metallo-endopeptidase | url = https://www.ncbi.nlm.nih.gov/gene/4311 }}</ref> It also degrades the [[amyloid beta]] peptide whose abnormal [[protein folding|misfolding]] and aggregation in [[neural tissue]] has been implicated as a cause of [[Alzheimer's disease]]. Synthesized as a [[membrane protein|membrane-bound protein]], the neprilysin ectodomain is released into the extracellular domain after it has been transported from the [[Golgi apparatus]] to the cell surface.

Neprilysin is expressed in a wide variety of tissues and is particularly abundant in kidney. It is also a common [[acute lymphocytic leukemia]] antigen that is an important cell surface marker in the diagnosis of human acute lymphocytic leukemia (ALL). This protein is present on leukemic cells of pre-B phenotype, which represent 85% of cases of ALL.<ref name="entrez"/>

Hematopoetic progenitors expressing CD10 are considered "common lymphoid progenitors", which means they can differentiate into T, B or natural killer cells.<ref>{{cite journal | pmid = 7584137 | volume=3 | issue=4 | title=Human T, B, natural killer, and dendritic cells arise from a common bone marrow progenitor cell subset. | date=Oct 1995 | journal=Immunity | pages=459–73 | doi=10.1016/1074-7613(95)90175-2}}</ref> CD10 is of use in hematological diagnosis since it is expressed by early B, pro-B and pre-B lymphocytes, and by lymph node [[germinal centers]].<ref name="urlCD Markers - CD10">{{cite web | url = http://www.pathologyoutlines.com/topic/cdmarkerscd10.html | title = CD10 | author = Singh C | date = 2011-02-25 | work = CD Markers | publisher = PathologyOutlines.com, Inc. }}</ref> Hematologic diseases in which it is positive include ALL, [[angioimmunoblastic T cell lymphoma]],  [[Burkitt lymphoma]],  [[chronic myelogenous leukemia]] in blast crisis (90%),  [[diffuse large B-cell lymphoma]] (variable),  follicular center cells (70%),  [[hairy cell leukemia]] (10%), and myeloma (some). It tends to be negative in [[acute myeloid leukemia]], [[chronic lymphocytic leukemia]], [[mantle cell lymphoma]], and [[marginal zone lymphoma]]. CD10 is found on non-T ALL cells, which derive from pre-B lymphocytes, and in germinal center-related non-Hodgkin lymphoma such as Burkitt lymphoma and follicular lymphoma, but not on leukemia cells or lymphomas, which originate in more mature B cells.<ref name="pmid20051779">{{cite journal |vauthors=Papandreou CN, Nanus DM | title = Is methylation the key to CD10 loss? | journal = J. Pediatr. Hematol. Oncol. | volume = 32 | issue = 1 | pages = 2–3 |date=January 2010 | pmid = 20051779 | doi = 10.1097/MPH.0b013e3181c74aca  }}</ref>

== Amyloid beta regulation ==
Neprilysin-deficient [[knockout mouse|knockout mice]] show both Alzheimer's-like behavioral impairment and amyloid-beta deposition in the brain,<ref name="Madani">{{cite journal |vauthors=Madani R, Poirier R, Wolfer DP, Welzl H, Groscurth P, Lipp HP, Lu B, El Mouedden M, Mercken M, Nitsch RM, Mohajeri MH | title = Lack of neprilysin suffices to generate murine amyloid-like deposits in the brain and behavioral deficit in vivo | journal = J. Neurosci. Res. | volume = 84 | issue = 8 | pages = 1871–8 |date=December 2006 | pmid = 16998901 | doi = 10.1002/jnr.21074 }}</ref> providing strong evidence for the protein's association with the Alzheimer's disease process. Because neprilysin is thought to be the [[rate-limiting step]] in amyloid beta degradation,<ref name="Iwata1">{{cite journal |vauthors=Iwata N, Tsubuki S, Takaki Y, Watanabe K, Sekiguchi M, Hosoki E, Kawashima-Morishima M, Lee HJ, Hama E, Sekine-Aizawa Y, Saido TC | title = Identification of the major Abeta1-42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition | journal = Nat. Med. | volume = 6 | issue = 2 | pages = 143–50 |date=February 2000 | pmid = 10655101 | doi = 10.1038/72237 }}</ref> it has been considered a potential therapeutic target; compounds such as the [[peptide hormone]] [[somatostatin]] have been identified that increase the enzyme's activity level.<ref name="Iwata">{{cite journal |vauthors=Iwata N, Higuchi M, Saido TC | title = Metabolism of amyloid-beta peptide and Alzheimer's disease | journal = Pharmacol. Ther. | volume = 108 | issue = 2 | pages = 129–48 |date=November 2005 | pmid = 16112736 | doi = 10.1016/j.pharmthera.2005.03.010 }}</ref> One hypothesis for the strong dependence of Alzheimer's incidence on age focuses on the declining production of somatostatin in the brains of elderly people, which thus depresses the activity of neprilysin and promotes aggregation of unprocessed amyloid beta.<ref name="Hama">{{cite journal |vauthors=Hama E, Saido TC | title = Etiology of sporadic Alzheimer's disease: somatostatin, neprilysin, and amyloid beta peptide | journal = Med. Hypotheses | volume = 65 | issue = 3 | pages = 498–500 | year = 2005 | pmid = 15921860 | doi = 10.1016/j.mehy.2005.02.045 }}</ref> Declining neprilysin activity with increasing age may also be explained by [[oxidative]] damage, known to be a causative factor in Alzheimer's disease; higher levels of inappropriately oxidized neprilysin have been found in Alzheimer's patients compared to cognitively normal elderly people.<ref name="Wang">{{cite journal |vauthors=Wang DS, Iwata N, Hama E, Saido TC, Dickson DW | title = Oxidized neprilysin in aging and Alzheimer's disease brains | journal = Biochem. Biophys. Res. Commun. | volume = 310 | issue = 1 | pages = 236–41 |date=October 2003 | pmid = 14511676 | doi = 10.1016/j.bbrc.2003.09.003 }}</ref>

== Signaling peptides ==
[[Image:Kidney cd10 ihc.jpg|thumb|Neprilysin immunohistochemical staining of normal [[kidney]].]]
Neprilysin is also associated with other biochemical processes, and is particularly highly expressed in [[kidney]] and [[lung]] tissues. Inhibitors have been designed with the aim of developing [[analgesic]] and [[antihypertensive]] agents that act by preventing neprilysin's activity against signaling peptides such as [[enkephalin]]s, [[substance P]], [[endothelin]], and [[atrial natriuretic peptide]].<ref name="Sahli">{{cite journal |vauthors=Sahli S, Stump B, Welti T, Schweizer WB, Diederich R, Blum-Kaelin D, Aebi JD, Böhm HJ |date=April 2005 |title=A New Class of Inhibitors for the Metalloprotease Neprilysin Based on a Central Imidazole Scaffold |journal=[[Helvetica Chimica Acta]] |volume=88 |issue=4 |pages=707–730 |doi=10.1002/hlca.200590050 }}</ref><ref name="Oefner">{{cite journal |vauthors=Oefner C, Roques BP, Fournie-Zaluski MC, Dale GE | title = Structural analysis of neprilysin with various specific and potent inhibitors | journal = Acta Crystallogr. D | volume = 60 | issue = Pt 2 | pages = 392–6 |date=February 2004 | pmid = 14747736 | doi = 10.1107/S0907444903027410 }}</ref>

Associations have been observed between neprilysin expression and various types of [[cancer]]; however, the relationship between neprilysin expression and carcinogenesis remains obscure. In cancer [[biomarker]] studies, the neprilysin gene is often referred to as CD10 or CALLA. In some types of cancer, such as [[metastatic]] [[carcinoma]] and some advanced [[melanoma]]s, neprilysin is overexpressed;<ref name="Velazquez">{{cite journal |vauthors=Velazquez EF, Yancovitz M, Pavlick A, Berman R, Shapiro R, Bogunovic D, O'Neill D, Yu YL, Spira J, Christos PJ, Zhou XK, Mazumdar M, Nanus DM, Liebes L, Bhardwaj N, Polsky D, Osman I | title = Clinical relevance of neutral endopeptidase (NEP/CD10) in melanoma | journal = J Transl Med | volume = 5 | issue = 1| pages = 2 | year = 2007 | pmid = 17207277 | pmc = 1770905 | doi = 10.1186/1479-5876-5-2 }}</ref> in other types, most notably [[lung cancer]]s, neprilysin is downregulated, and thus unable to modulate the pro-growth [[autocrine]] signaling of cancer cells via secreted peptides such as mammalian [[homology (biology)|homologs]] related to [[bombesin]].<ref name="Cohen">{{cite journal |vauthors=Cohen AJ, Bunn PA, Franklin W, Magill-Solc C, Hartmann C, Helfrich B, Gilman L, Folkvord J, Helm K, Miller YE | title = Neutral endopeptidase: variable expression in human lung, inactivation in lung cancer, and modulation of peptide-induced calcium flux | journal = Cancer Res. | volume = 56 | issue = 4 | pages = 831–9 |date=February 1996 | pmid = 8631021 | doi = | url = http://cancerres.aacrjournals.org/cgi/reprint/56/4/831 }}</ref>
Some plant extracts (methanol extracts of ''[[Ceropegia]] rupicola'', ''[[Kniphofia]] sumarae'', '' [[Plectranthus]] cf barbatus'', and an aqueous extract of ''[[Pavetta]] longiflora'') were found able to inhibit the enzymatic activity of neutral endopeptidase.<ref name="pmid18271311">{{cite journal |vauthors=Alasbahi R, Melzig MF | title = Screening of some Yemeni medicinal plants for inhibitory activity against peptidases | journal = Pharmazie | volume = 63 | issue = 1 | pages = 86–8 |date=January 2008 | pmid = 18271311 | doi = }}</ref>

== Inhibitors ==
Inhibitors have been designed with the aim of developing [[analgesic]] and [[antihypertensive]] agents that act by preventing neprilysin's activity against signaling peptides such as [[enkephalin]]s, [[substance P]], [[endothelin]], and [[atrial natriuretic peptide]].<ref name="Sahli"/><ref name="Oefner"/>

Some are intended to treat [[heart failure]].<ref name=McMurray2014/>

* [[Sacubitril/valsartan]] (Entresto/LCZ696), which has been tested against [[enalapril]] in patients with heart failure.<ref name=McMurray2014>{{cite journal | vauthors = McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR | title = Angiotensin-neprilysin inhibition versus enalapril in heart failure | journal = The New England Journal of Medicine | volume = 371 | issue = 11 | pages = 993–1004 | date = Sep 2014 | pmid = 25176015 | doi = 10.1056/NEJMoa1409077 | url = http://www.nejm.org/doi/full/10.1056/NEJMoa1409077 }}</ref>
* [[Sacubitril]] (AHU-377), a [[prodrug]] which is a component of [[sacubitril/valsartan]]
* [[Sacubitrilat]] (LBQ657), the active form of sacubitril
* [[RB-101]], an enkephalinase inhibitor, used in scientific research.
* [[UK-414,495]]
* [[Omapatrilat]] (dual inhibitor of NEP and [[angiotensin-converting enzyme]]) developed by BMS did not receive FDA approval due to [[angioedema]] safety concerns.
* [[Ecadotril]]

Other dual inhibitors of NEP with ACE/angiotensin receptor are (in 2003) being developed by pharmaceutical companies.<ref>{{cite journal |author=Venugopal J |title=Pharmacological modulation of the natriuretic peptide system |journal=Expert Opinion on Therapeutic Patents |volume=13 |issue=9 |pages=1389–1409 |year=2003 |url=http://www.expertopin.com/doi/abs/10.1517/13543776.13.9.1389 |doi=10.1517/13543776.13.9.1389}}</ref>

== Immunochemistry ==
CD10 is used in clinical pathology for diagnostic purpose.

=== In lymphomas and leukemias ===
* [[Acute lymphoblastic leukemia]] (ALL) cells are CD10<sup>+</sup>.
* [[Follicular lymphoma]] (follicle centre cell lymphoma) are CD10<sup>+</sup>.
* Burkitt Lymphoma cells are CD10<sup>+</sup>.
* CD10<sup>+</sup> diffuse large B cell lymphoma (CD10<sup>+</sup> DLBLC)<ref name="pmid22431545">{{cite journal |vauthors=McGowan P, Nelles N, Wimmer J, Williams D, Wen J, Li M, Ewton A, Curry C, Zu Y, Sheehan A, Chang CC | title = Differentiating between Burkitt lymphoma and CD10+ diffuse large B-cell lymphoma: the role of commonly used flow cytometry cell markers and the application of a multiparameter scoring system | journal = Am. J. Clin. Pathol. | volume = 137 | issue = 4 | pages = 665–70 | year = 2012 | pmid = 22431545 | doi = 10.1309/AJCP3FEPX5BEEKGX | pmc = 4975158 }}</ref>
** Marker for germinal center phenotype (CD10, HGAL, BCL6, CD38) are considered a favorable prognostic factor,<ref name="pmid15920553">{{cite journal |vauthors=Berglund M, Thunberg U, Amini RM, Book M, Roos G, Erlanson M, Linderoth J, Dictor M, Jerkeman M, Cavallin-Ståhl E, Sundström C, Rehn-Eriksson S, Backlin C, Hagberg H, Rosenquist R, Enblad G | title = Evaluation of immunophenotype in diffuse large B-cell lymphoma and its impact on prognosis | journal = Mod. Pathol. | volume = 18 | issue = 8 | pages = 1113–20 | year = 2005 | pmid = 15920553 | doi = 10.1038/modpathol.3800396 }}</ref><ref name="pmid20309427">{{cite journal |vauthors=Höller S, Horn H, Lohr A, Mäder U, Katzenberger T, Kalla J, Bernd HW, Went P, Ott MM, Müller-Hermelink HK, Rosenwald A, Ott G | title = A cytomorphological and immunohistochemical profile of aggressive B-cell lymphoma: high clinical impact of a cumulative immunohistochemical outcome predictor score | journal = J Hematopathol | volume = 2 | issue = 4 | pages = 187–94 | year = 2009 | pmid = 20309427 | pmc = 2798934 | doi = 10.1007/s12308-009-0044-x }}</ref> but CD10<sup>+</sup>, [[BCL2]]<sup>+ </sup>tumors could have poorer survival.<ref name="pmid11488064">{{cite journal |vauthors=Xu Y, McKenna RW, Molberg KH, Kroft SH | title = Clinicopathologic analysis of CD10+ and CD10- diffuse large B-cell lymphoma. Identification of a high-risk subset with coexpression of CD10 and bcl-2 | journal = Am. J. Clin. Pathol. | volume = 116 | issue = 2 | pages = 183–90 | year = 2001 | pmid = 11488064 | doi = 10.1309/J7RN-UXAY-55GX-BUNK }}</ref> For some authors, CD10 expression in DLBCL does not influence survival.<ref name="pmid15517363">{{cite journal |vauthors=Fabiani B, Delmer A, Lepage E, Guettier C, Petrella T, Brière J, Penny AM, Copin MC, Diebold J, Reyes F, Gaulard P, Molina TJ | title = CD10 expression in diffuse large B-cell lymphomas does not influence survival | journal = Virchows Arch. | volume = 445 | issue = 6 | pages = 545–51 | year = 2004 | pmid = 15517363 | doi = 10.1007/s00428-004-1129-7 }}</ref>
* [[Angioimmunoblastic T cell lymphoma]] (AITL) are CD10<sup>+</sup><ref name="pmid21499231">{{cite journal |vauthors=Baseggio L, Traverse-Glehen A, Berger F, Ffrench M, Jallades L, Morel D, Goedert G, Magaud JP, Salles G, Felman P | title = CD10 and ICOS expression by multiparametric flow cytometry in angioimmunoblastic T-cell lymphoma | journal = Mod. Pathol. | volume = 24 | issue = 7 | pages = 993–1003 | year = 2011 | pmid = 21499231 | doi = 10.1038/modpathol.2011.53 }}</ref><ref name="pmid16084948">{{cite journal |vauthors=Yuan CM, Vergilio JA, Zhao XF, Smith TK, Harris NL, Bagg A | title = CD10 and BCL6 expression in the diagnosis of angioimmunoblastic T-cell lymphoma: utility of detecting CD10+ T cells by flow cytometry | journal = Hum. Pathol. | volume = 36 | issue = 7 | pages = 784–91 | year = 2005 | pmid = 16084948 | doi = 10.1016/j.humpath.2005.05.008 }}</ref> and distinguishes AITL from other T cell lymphomas (CD10<sup>−</sup>)<ref name="pmid14707864">{{cite journal |vauthors=Attygalle AD, Diss TC, Munson P, Isaacson PG, Du MQ, Dogan A | title = CD10 expression in extranodal dissemination of angioimmunoblastic T-cell lymphoma | journal = Am. J. Surg. Pathol. | volume = 28 | issue = 1 | pages = 54–61 | year = 2004 | pmid = 14707864 | doi = 10.1097/00000478-200401000-00005}}</ref>
** Some benign T cells can be CD10<sup>+</sup><ref name="pmid13679451">{{cite journal |vauthors=Cook JR, Craig FE, Swerdlow SH | title = Benign CD10-positive T cells in reactive lymphoid proliferations and B-cell lymphomas | journal = Mod. Pathol. | volume = 16 | issue = 9 | pages = 879–85 | year = 2003 | pmid = 13679451 | doi = 10.1097/01.MP.0000084630.64243.D1 }}</ref>

=== In epithelial tumors ===
* [[Clear cell renal cell carcinoma]] (Clear cell RCC)
** CD10<sup>+</sup> distinguishes renal cell carcinoma, conventional type with eosinophilic morphology from its mimickers. Chromophobe carcinoma and oncocytoma are CD10<sup>−</sup>.<ref name="pmid22417859">{{cite journal |vauthors=Yasir S, Herrera L, Gomez-Fernandez C, Reis IM, Umar S, Leveillee R, Kava B, Jorda M | title = CD10<sup>+</sup> and CK7/RON- immunophenotype distinguishes renal cell carcinoma, conventional type with eosinophilic morphology from its mimickers | journal = Appl. Immunohistochem. Mol. Morphol. | volume = 20 | issue = 5 | pages = 454–61 | year = 2012 | pmid = 22417859 | doi = 10.1097/PAI.0b013e31823fecd3 }}</ref>
* [[Pancreatic tumor]]s
** [[Solid pseudopapillary tumour]]s are CD10<sup>+</sup>.<ref name="pmid11023097">{{cite journal |vauthors=Notohara K, Hamazaki S, Tsukayama C, Nakamoto S, Kawabata K, Mizobuchi K, Sakamoto K, Okada S | title = Solid-pseudopapillary tumor of the pancreas: immunohistochemical localization of neuroendocrine markers and CD10 | journal = Am. J. Surg. Pathol. | volume = 24 | issue = 10 | pages = 1361–71 | year = 2000 | pmid = 11023097 | doi = 10.1097/00000478-200010000-00005}}</ref>
** CD10<sup>+</sup> differentiates [[mucinous cystic neoplasm]]s (CD10<sup>+</sup>/CK20+) from [[intraductal papillary mucinous neoplasm]] of branch duct type (CD10<sup>−</sup>/CK20-).<ref name="pmid11023097"/>
* [[Cutaneous tumor]]s
** CD10 may differentiate [[basal cell carcinoma]] (CD10 epithelial staining) from [[trichoblastoma]] (CD10 peritumoral stromal staining), basal cell carcinoma with follicular differentiation (CD10 stromal and epithelial staining)<ref name="pmid19570076">{{cite journal |vauthors=Córdoba A, Guerrero D, Larrinaga B, Iglesias ME, Arrechea MA, Yanguas JI | title = Bcl-2 and CD10 expression in the differential diagnosis of trichoblastoma, basal cell carcinoma, and basal cell carcinoma with follicular differentiation | journal = Int. J. Dermatol. | volume = 48 | issue = 7 | pages = 713–7 | year = 2009 | pmid = 19570076 | doi = 10.1111/j.1365-4632.2009.04076.x }}</ref> and [[squamous cell carcinoma]] (strong stromal staining).<ref name="pmid23825889">{{cite journal |vauthors=Sari Aslani F, Akbarzadeh-Jahromi M, Jowkar F | title = Value of CD10 Expression in Differentiating Cutaneous Basal from Squamous Cell Carcinomas and Basal Cell Carcinoma from Trichoepithelioma | journal = Iran J Med Sci | volume = 38 | issue = 2 | pages = 100–6 | year = 2013 | pmid = 23825889 | pmc = 3700055 | doi = }}</ref>
** CD10 differentiates CD10<sup>+</sup> [[atypical fibroxanthoma]] from CD10<sup>−</sup> spindle cell [[melanoma]] and sarcomatoid [[squamous cell carcinoma]].
* [[Urothelial tumor]]s express CD10 (42-67%).<ref name="pmid16191505">{{cite journal |vauthors=Murali R, Delprado W | title = CD10 immunohistochemical staining in urothelial neoplasms | journal = Am. J. Clin. Pathol. | volume = 124 | issue = 3 | pages = 371–9 | year = 2005 | pmid = 16191505 | doi = 10.1309/04BH-F6A8-0BQM-H7HT }}</ref>
** CD10 expression is strongly correlated with high tumor grade and stage in urothelial carcinoma of the bladder. CD10 may be associated with tumor progression in bladder cancer pathogenesis.<ref name="pmid19917108">{{cite journal |vauthors=Bahadir B, Behzatoglu K, Bektas S, Bozkurt ER, Ozdamar SO | title = CD10 expression in urothelial carcinoma of the bladder | journal = Diagn Pathol | volume = 4 | issue = 1| pages = 38 | year = 2009 | pmid = 19917108 | pmc = 2780995 | doi = 10.1186/1746-1596-4-38 }}</ref>

=== In other tumors === 
* CD10 expression might be one of the characteristics of müllerian system-derived neoplastic mesenchymal cells.<ref name="pmid12218209">{{cite journal |vauthors=Mikami Y, Hata S, Kiyokawa T, Manabe T | title = Expression of CD10 in malignant müllerian mixed tumors and adenosarcomas: an immunohistochemical study | journal = Mod. Pathol. | volume = 15 | issue = 9 | pages = 923–30 | year = 2002 | pmid = 12218209 | doi = 10.1097/01.MP.0000026058.33869.DB }}</ref>
** Normal endometrial stroma<ref name="pmid11532038">{{cite journal |vauthors=McCluggage WG, Sumathi VP, Maxwell P | title = CD10 is a sensitive and diagnostically useful immunohistochemical marker of normal endometrial stroma and of endometrial stromal neoplasms | journal = Histopathology | volume = 39 | issue = 3 | pages = 273–8 | year = 2001 | pmid = 11532038 | doi = 10.1046/j.1365-2559.2001.01215.x}}</ref>
** [[Endometrial stromal sarcoma]] (ESS) are CD10<sup>+</sup> ([[Smooth muscle tumor]]s are usually CD10<sup>−</sup>,<ref name="pmid15867200">{{cite journal |vauthors=Kabbinavar FF, Hambleton J, Mass RD, Hurwitz HI, Bergsland E, Sarkar S | title = Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer | journal = J. Clin. Oncol. | volume = 23 | issue = 16 | pages = 3706–12 | year = 2005 | pmid = 15867200 | doi = 10.1200/JCO.2005.00.232 }}</ref> but can be CD10<sup>+</sup> <ref name="pmid12218209"/>
** [[Malignant müllerian mixed tumor]] (MMMT)
** [[Müllerian adenosarcoma]]
** [[Uterine high-grade leiomyosarcoma]]
** [[Uterine rhabdomyosarcoma]]
* Vascular tumors
** [[Epithelioid hemangioendothelioma]] are mostly CD10<sup>+</sup>.<ref name="pmid19961253">{{cite journal |vauthors=Weinreb I, Cunningham KS, Perez-Ordoñez B, Hwang DM | title = CD10 is expressed in most epithelioid hemangioendotheliomas: a potential diagnostic pitfall | journal = Arch. Pathol. Lab. Med. | volume = 133 | issue = 12 | pages = 1965–8 | year = 2009 | pmid = 19961253 | doi = 10.1043/1543-2165-133.12.1965 }}</ref>
** [[Hemangioblastoma]] is usually CD10<sup>−</sup> (metastatic [[renal cell carcinoma]] is CD10<sup>+</sup>)<ref name="pmid15578072">{{cite journal |vauthors=Jung SM, Kuo TT | title = Immunoreactivity of CD10 and inhibin alpha in differentiating hemangioblastoma of central nervous system from metastatic clear cell renal cell carcinoma | journal = Mod. Pathol. | volume = 18 | issue = 6 | pages = 788–94 | year = 2005  | pmid = 15578072 | doi = 10.1038/modpathol.3800351 }}</ref><ref name="pmid22497861">{{cite journal |vauthors=Yin WH, Li J, Chan JK | title = Sporadic haemangioblastoma of the kidney with rhabdoid features and focal CD10 expression: report of a case and literature review | journal = Diagn Pathol | volume = 7 | issue = 1| pages = 39 | year = 2012 | pmid = 22497861 | pmc = 3364142 | doi = 10.1186/1746-1596-7-39 }}</ref>

== See also ==
* [[List of histologic stains that aid in diagnosis of cutaneous conditions]]

== References ==
{{Reflist|2}}

== External links ==
* The [[MEROPS]] online database for peptidases and their inhibitors: [http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=M13.001 M13.001]
* {{MeshName|Neprilysin}}

{{NLM content}}
{{PDB_Gallery|geneid=4311}}
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{{Clusters of differentiation by lineage}}
{{Tumor markers}}
{{Metalloendopeptidases}}
{{Enzymes}}
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[[Category:Alzheimer's disease]]
[[Category:EC 3.4.24]]
[[Category:Tumor markers]]