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Immunophenotypic profile of biomarkers related to anti-apoptotic and neural development pathways in the Ewing's family of tumors (EFT) and their therapeutic implications.
Anticancer Res. 2007 Jul-Aug; 27(4B):2457-63.AR

Abstract

BACKGROUND

Ewing's family of tumors (EFT) comprises a broad spectrum of tumors composed of primitive committed cells with neuroectodermal capacity. The degree of neural differentiation within EFT, as measured with morphological features and expression of neural markers, delimits two members: Ewing's sarcoma (ES) and peripheral primitive neuroectodermal tumor (pPNET). Molecules such as c-kit and its ligand (Stem cell factor, SCF), CD95 (FAS), CD95L (FASL), IGF-IR, protect EFT cells from apoptosis, whereas c-erb-B2, erythropoietin (EPO) and its receptor (EPO-R) participate in the maturation of primitive committed neuroectodermal cells and in the normal embryonal brain development. The aim of the present study was to analyse the expression of these molecules in paraffin-embedded material from a series of EFT.

MATERIALS AND METHODS

Forty-five cases of EFT (23 typical ES, 4 atypical and 18 pPNET) were analysed following the immunohistochemical LSAB method, with antigen retrieval heating using an autoclave, citrate buffer pH 6.0 and the following primary antibodies: FAS (APO-CD 95), FAS-L, c-kit, SCF, IGF-IR and c-erbB2. The expression was evaluated independently by three of the authors and the final score (0 to 3+) was based on the intensity and percentage of positively stained cells. In a second cooperative analysis, tissues from 30 cases of EFT (15 typical, 3 atypical and 12 PNET) were immunostained with EPO and EPO-R.

RESULTS

High expression of c-kit/SCF (2+, 3+) was detected in 28/45 cases of EFT (62.2%), whereas FAS-FAS-L and IGF-IR were observed in 16/45 (37.7%) and 9/45 (20%), respectively. Regarding the neuroectodermal pathway, membranous and cytoplasmic expression of c-erb-B2 was observed in 9/45 (20%) EFT, regardless of the morphological and immunohistochemical expression of conventional neural markers. High expression of EPO and EPO-R was observed in 20/30 EFT (66.6%).

CONCLUSION

C-kit/SCF and EPO/EPO-R seem to participate in the pathway of anti-apoptotic and proliferative advantage, while c-erb-B2 does not play an important role in the neuroectodermal differentiation pathway in EFT cells.

Authors+Show Affiliations

Department of Pathology, Medical School, University of Valencia, Spain.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
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17695539

Citation

Navarro, S, et al. "Immunophenotypic Profile of Biomarkers Related to Anti-apoptotic and Neural Development Pathways in the Ewing's Family of Tumors (EFT) and Their Therapeutic Implications." Anticancer Research, vol. 27, no. 4B, 2007, pp. 2457-63.
Navarro S, Giraudo P, Karseladze AI, et al. Immunophenotypic profile of biomarkers related to anti-apoptotic and neural development pathways in the Ewing's family of tumors (EFT) and their therapeutic implications. Anticancer Res. 2007;27(4B):2457-63.
Navarro, S., Giraudo, P., Karseladze, A. I., Smirnov, A., Petrovichev, N., Savelov, N., Alvarado-Cabrero, I., & Llombart-Bosch, A. (2007). Immunophenotypic profile of biomarkers related to anti-apoptotic and neural development pathways in the Ewing's family of tumors (EFT) and their therapeutic implications. Anticancer Research, 27(4B), 2457-63.
Navarro S, et al. Immunophenotypic Profile of Biomarkers Related to Anti-apoptotic and Neural Development Pathways in the Ewing's Family of Tumors (EFT) and Their Therapeutic Implications. Anticancer Res. 2007 Jul-Aug;27(4B):2457-63. PubMed PMID: 17695539.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunophenotypic profile of biomarkers related to anti-apoptotic and neural development pathways in the Ewing's family of tumors (EFT) and their therapeutic implications. AU - Navarro,S, AU - Giraudo,P, AU - Karseladze,A I, AU - Smirnov,A, AU - Petrovichev,N, AU - Savelov,N, AU - Alvarado-Cabrero,I, AU - Llombart-Bosch,A, PY - 2007/8/19/pubmed PY - 2007/9/7/medline PY - 2007/8/19/entrez SP - 2457 EP - 63 JF - Anticancer research JO - Anticancer Res. VL - 27 IS - 4B N2 - BACKGROUND: Ewing's family of tumors (EFT) comprises a broad spectrum of tumors composed of primitive committed cells with neuroectodermal capacity. The degree of neural differentiation within EFT, as measured with morphological features and expression of neural markers, delimits two members: Ewing's sarcoma (ES) and peripheral primitive neuroectodermal tumor (pPNET). Molecules such as c-kit and its ligand (Stem cell factor, SCF), CD95 (FAS), CD95L (FASL), IGF-IR, protect EFT cells from apoptosis, whereas c-erb-B2, erythropoietin (EPO) and its receptor (EPO-R) participate in the maturation of primitive committed neuroectodermal cells and in the normal embryonal brain development. The aim of the present study was to analyse the expression of these molecules in paraffin-embedded material from a series of EFT. MATERIALS AND METHODS: Forty-five cases of EFT (23 typical ES, 4 atypical and 18 pPNET) were analysed following the immunohistochemical LSAB method, with antigen retrieval heating using an autoclave, citrate buffer pH 6.0 and the following primary antibodies: FAS (APO-CD 95), FAS-L, c-kit, SCF, IGF-IR and c-erbB2. The expression was evaluated independently by three of the authors and the final score (0 to 3+) was based on the intensity and percentage of positively stained cells. In a second cooperative analysis, tissues from 30 cases of EFT (15 typical, 3 atypical and 12 PNET) were immunostained with EPO and EPO-R. RESULTS: High expression of c-kit/SCF (2+, 3+) was detected in 28/45 cases of EFT (62.2%), whereas FAS-FAS-L and IGF-IR were observed in 16/45 (37.7%) and 9/45 (20%), respectively. Regarding the neuroectodermal pathway, membranous and cytoplasmic expression of c-erb-B2 was observed in 9/45 (20%) EFT, regardless of the morphological and immunohistochemical expression of conventional neural markers. High expression of EPO and EPO-R was observed in 20/30 EFT (66.6%). CONCLUSION: C-kit/SCF and EPO/EPO-R seem to participate in the pathway of anti-apoptotic and proliferative advantage, while c-erb-B2 does not play an important role in the neuroectodermal differentiation pathway in EFT cells. SN - 0250-7005 UR - https://www.unboundmedicine.com/medline/citation/17695539/Immunophenotypic_profile_of_biomarkers_related_to_anti_apoptotic_and_neural_development_pathways_in_the_Ewing's_family_of_tumors__EFT__and_their_therapeutic_implications_ L2 - http://ar.iiarjournals.org/cgi/pmidlookup?view=long&pmid=17695539 DB - PRIME DP - Unbound Medicine ER -