Abstract
The neural cell adhesion molecule L1 (CD171) is a multidomain type 1 membrane glycoprotein of the immunoglobulin superfamily important in the nervous system development, kidney morphogenesis, and maintenance of the immune system. Recent studies reported CD171 expression being associated with adverse clinical outcome in different types of cancer and there has been a growing interest in targeting this cell membrane molecule on neoplastic cells by chimeric antigen receptor redirected T lymphocytes or specific antibodies. Nevertheless, conflicting results regarding the prognostic value of CD171 expression in renal cell carcinomas and gastrointestinal stromal tumors were published. In this study, CD171 expression was immunohistochemically analyzed in 5155 epithelial, mesenchymal, melanocytic, and lymphohematopoietic tumors to assess its utility in diagnostic pathology and to pinpoint potential targets for CD171-targeting therapy. A newly developed anti-CD171 rabbit monoclonal antibody, clone 014, was selected from the panel of commercially available CD171 antibodies. Immunohistochemistry was performed using Leica Bond Max automation and multitumor blocks containing up to 60 tumor samples. CD171 was constitutively and strongly expressed in neuroectodermal tumors such as schwannoma, neuroblastoma, and paraganglioma, whereas other mesenchymal tumors including schwannoma mimics showed only rarely CD171 positivity. Frequent CD171-expression was also detected in ovarian serous carcinoma, malignant mesothelioma, and testicular embryonal carcinoma. CD171 immunohistochemistry may have some role in immunophenotypic differential diagnosis of neurogenic tumors and pinpointing potential candidates for anti-CD171 therapy. Though, because of its rare expression and lack of predictive value, CD171 is neither a diagnostic nor prognostic marker for gastrointestinal stromal tumors.
Highlights
[2] CD171 is the member of the L1-family of closely related neural cell adhesion molecules (CAMs). [3] CD171 can bind to itself or heterophilically to other molecules including integrins, CD24, neurocan, neuropilin-1, and other members of the L1 family for signal transduction. [4, 5] The cytoplasmic tail of CD171 can interact with other cytoplasmic proteins such as ankyrin, actin, spectrin, and www.impactjournals.com/oncotarget ezrin-radixin-moesin (ERM) proteins
CD171 plays an important role in neural development for myelination, fasciculation, axon guidance, and migration of granule cells in cerebellar cortex. [10,11,12] Consistent with an important role of CD171 in central nervous system (CNS) development, CD171 mutations lead to variable abnormalities including mental retardation and anomaly of CNS, referred to as CRASH syndrome. [5, 13] Outside the nervous system, CD171 appears to be important for kidney morphogenesis [14] and interactions between leukocytes and endothelial cells. [15]
CD171 was first identified in the CNS of the mouse as a neural cell adhesion molecule
Summary
The neural cell adhesion molecule L1 (CD171, NCAM-L1, L1CAM) was first identified in the central nervous system (CNS) of the mouse. [1] CD171 is a multidomain type 1 transmembrane glycoprotein of the immunoglobulin superfamily composed of six Ig-like domains, five fibronectin type III repeats, transmembrane region, and a highly conserved cytoplasmic tail. [2] CD171 is the member of the L1-family of closely related neural cell adhesion molecules (CAMs). [3] CD171 can bind to itself (homophilic) or heterophilically to other molecules including integrins, CD24, neurocan, neuropilin-1, and other members of the L1 family for signal transduction. [4, 5] The cytoplasmic tail of CD171 can interact with other cytoplasmic proteins such as ankyrin, actin, spectrin, and www.impactjournals.com/oncotarget ezrin-radixin-moesin (ERM) proteins. [6] It is reported that CD171 is enzymatically cleaved by a disintegrin and metalloproteinase (ADAM) and extra cellular domains were detectable as a soluble form in the blood. [7,8,9]CD171 plays an important role in neural development for myelination, fasciculation, axon guidance, and migration of granule cells in cerebellar cortex. [10,11,12] Consistent with an important role of CD171 in CNS development, CD171 mutations lead to variable abnormalities including mental retardation and anomaly of CNS, referred to as CRASH (corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraplegia and hydrocephalus) syndrome. [5, 13] Outside the nervous system, CD171 appears to be important for kidney morphogenesis [14] and interactions between leukocytes and endothelial cells. [15]Recently, several studies showed that overexpression of CD171 in ovarian, endometrial, colorectal and nonsmall cell lung carcinomas correlates with worse clinical outcome. [16,17,18,19] In addition, there has been growing interest in targeting this cell membrane molecule on neoplastic cells by chimeric antigen receptor redirected T lymphocytes or specific antibodies. [20,21,22,23,24,25] immunohistochemical data on CD171 expression in germ cell, rare gastrointesitinal and peripheral mesenchymal tumors as well as lymphohematopoietic tumors remains incomplete. The neural cell adhesion molecule L1 (CD171, NCAM-L1, L1CAM) was first identified in the central nervous system (CNS) of the mouse. [2] CD171 is the member of the L1-family of closely related neural cell adhesion molecules (CAMs). CD171 plays an important role in neural development for myelination, fasciculation, axon guidance, and migration of granule cells in cerebellar cortex. Conflicting data regarding CD171 expression and its prognostic value were reported in renal cell cancers (RCCs) [26,27,28] and gastrointestinal stromal tumors (GISTs). The aim of this study was to evaluate potential utility of CD171 immunohistochemistry in diagnostic pathology and to identify additional tumor types for future CD171-targeting therapy Conflicting data regarding CD171 expression and its prognostic value were reported in renal cell cancers (RCCs) [26,27,28] and gastrointestinal stromal tumors (GISTs). [9, 29, 30]
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