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Intercellular junctions in Ewing sarcoma/primitive neuroectodermal tumor: additional evidence of epithelial differentiation.
Mod Pathol. 2005 Nov; 18(11):1403-10.MP

Abstract

Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) has recently been shown to frequently express cytokeratins, suggesting partial epithelial differentiation. Older ultrastructural studies have documented primitive cell-cell junctions in ES/PNET, reportedly resembling poorly formed desmosomes. Recently, paraffin-reactive antibodies have become available to proteins found in a variety of intercellular junctions indicative of epithelial differentiation, including tight junctions, desmosomes and adherens junctions. We examined intercellular junction protein expression in a large number of genetically confirmed ES/PNET. Formalin-fixed, paraffin-embedded sections from 23 primary and seven recurrent or metastatic cases of genetically confirmed ES/PNET were immunostained for claudin-1 and occludin (tight junction structural proteins), zonula occludens-1 (ZO-1, tight junction linker protein), desmoglein 1/2 (desmosomal adherens protein), desmoplakin (desmosomal structural protein) and E-cadherin (epithelial adherens junction protein), using steam heat-induced epitope retrieval and the Dako Envision system. Cases with >5% positive cells were scored as 'positive'. Normal colonic epithelium and skin served as external positive controls. Claudin-1 was expressed by 19 of 30 specimens (63%), ZO-1 was expressed by 15 of 29 specimens (51%), and occludin was expressed by three of 28 specimens (11%). In 28 specimens all three tight junction markers were evaluable. In all, 15 samples (54%) expressed only one tight junction marker, and 10 samples (36%) expressed two tight junction markers. No case expressed all three tight junction markers. Desmoglein was expressed in one of 30 (3%) samples. Desmoplakin was expressed in two of 28 (7%) samples. E-cadherin was negative in all cases. Our data suggest that many of the previously described cell-cell junctions in ES/PNET are poorly formed tight junctions, given the high frequency of claudin-1 and ZO-1 expression. This may underestimate the true frequency of tight junction protein expression in ES/PNET, as there are at least 20 different claudins and other ZO proteins. These tight junctions are almost certainly abnormal, given the absence of occludin expression in most cases. Desmosomal and adherens junction protein expression was rare to absent. Our findings provide additional evidence that ES/PNET frequently show partial epithelial differentiation.

Authors+Show Affiliations

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15920547

Citation

Schuetz, Audrey N., et al. "Intercellular Junctions in Ewing Sarcoma/primitive Neuroectodermal Tumor: Additional Evidence of Epithelial Differentiation." Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, vol. 18, no. 11, 2005, pp. 1403-10.
Schuetz AN, Rubin BP, Goldblum JR, et al. Intercellular junctions in Ewing sarcoma/primitive neuroectodermal tumor: additional evidence of epithelial differentiation. Mod Pathol. 2005;18(11):1403-10.
Schuetz, A. N., Rubin, B. P., Goldblum, J. R., Shehata, B., Weiss, S. W., Liu, W., Wick, M. R., & Folpe, A. L. (2005). Intercellular junctions in Ewing sarcoma/primitive neuroectodermal tumor: additional evidence of epithelial differentiation. Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, 18(11), 1403-10.
Schuetz AN, et al. Intercellular Junctions in Ewing Sarcoma/primitive Neuroectodermal Tumor: Additional Evidence of Epithelial Differentiation. Mod Pathol. 2005;18(11):1403-10. PubMed PMID: 15920547.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intercellular junctions in Ewing sarcoma/primitive neuroectodermal tumor: additional evidence of epithelial differentiation. AU - Schuetz,Audrey N, AU - Rubin,Brian P, AU - Goldblum,John R, AU - Shehata,Bahig, AU - Weiss,Sharon W, AU - Liu,Wendy, AU - Wick,Mark R, AU - Folpe,Andrew L, PY - 2005/5/28/pubmed PY - 2006/1/13/medline PY - 2005/5/28/entrez SP - 1403 EP - 10 JF - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JO - Mod. Pathol. VL - 18 IS - 11 N2 - Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) has recently been shown to frequently express cytokeratins, suggesting partial epithelial differentiation. Older ultrastructural studies have documented primitive cell-cell junctions in ES/PNET, reportedly resembling poorly formed desmosomes. Recently, paraffin-reactive antibodies have become available to proteins found in a variety of intercellular junctions indicative of epithelial differentiation, including tight junctions, desmosomes and adherens junctions. We examined intercellular junction protein expression in a large number of genetically confirmed ES/PNET. Formalin-fixed, paraffin-embedded sections from 23 primary and seven recurrent or metastatic cases of genetically confirmed ES/PNET were immunostained for claudin-1 and occludin (tight junction structural proteins), zonula occludens-1 (ZO-1, tight junction linker protein), desmoglein 1/2 (desmosomal adherens protein), desmoplakin (desmosomal structural protein) and E-cadherin (epithelial adherens junction protein), using steam heat-induced epitope retrieval and the Dako Envision system. Cases with >5% positive cells were scored as 'positive'. Normal colonic epithelium and skin served as external positive controls. Claudin-1 was expressed by 19 of 30 specimens (63%), ZO-1 was expressed by 15 of 29 specimens (51%), and occludin was expressed by three of 28 specimens (11%). In 28 specimens all three tight junction markers were evaluable. In all, 15 samples (54%) expressed only one tight junction marker, and 10 samples (36%) expressed two tight junction markers. No case expressed all three tight junction markers. Desmoglein was expressed in one of 30 (3%) samples. Desmoplakin was expressed in two of 28 (7%) samples. E-cadherin was negative in all cases. Our data suggest that many of the previously described cell-cell junctions in ES/PNET are poorly formed tight junctions, given the high frequency of claudin-1 and ZO-1 expression. This may underestimate the true frequency of tight junction protein expression in ES/PNET, as there are at least 20 different claudins and other ZO proteins. These tight junctions are almost certainly abnormal, given the absence of occludin expression in most cases. Desmosomal and adherens junction protein expression was rare to absent. Our findings provide additional evidence that ES/PNET frequently show partial epithelial differentiation. SN - 0893-3952 UR - https://www.unboundmedicine.com/medline/citation/15920547/Intercellular_junctions_in_Ewing_sarcoma/primitive_neuroectodermal_tumor:_additional_evidence_of_epithelial_differentiation_ L2 - http://dx.doi.org/10.1038/modpathol.3800435 DB - PRIME DP - Unbound Medicine ER -