Abstract
Epithelial marker and adhesion molecule expression has been reported in Ewing's sarcoma family of tumors (ESFTs), although the prognostic significance has not been assessed systematically. We performed immunohistochemical analysis of epithelial cell adhesion molecule and epithelial mesenchymal transition markers on 415 genetically confirmed ESFTs. Survival analyses were performed in 217 patients. The atypical histological subtype expressed a high proportion of the epithelial markers compared with conventional and PNET variants. We observed that expression of desmoplakin (p < 0.001) and PI3K (p = 0.003) was higher in disseminated than in localized disease. Multivariate analysis showed that desmoplakin and pGSK3β constitute independent good prognostic factors for progression free survival (PFS), while ZO-1 and Snail represent independent good prognostic factors for overall survival (OS). In contrast, CK8/18 represents an independent poor prognostic factor for OS and the radiotherapy treatment group demonstrated an independent poor prognostic factor for PFS and OS. Although the expression of pan-cytokeratin has been previously highlighted in a significant proportion of ESFT, its expression did not reveal prognostic significance in the present series. Considering the results of prognostic analysis herein reported, we strongly recommend a prospective validation of at least the immunomarkers with prognostic significance (desmoplakin, ZO-1, CK8/18, pGSK3β, and Snail) in prospective series that include localized and disseminated tumors.
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References
Folpe AL, Goldblum JR, Rubin BP, Shehata BM, Liu W, Dei Tos AP, Weiss SW (2005) Morphologic and immunophenotypic diversity in Ewing family tumors: a study of 66 genetically confirmed cases. Am J Surg Pathol 29(8):1025–1033
Gu M, Antonescu CR, Guiter G, Huvos AG, Ladanyi M, Zakowski MF (2000) Cytokeratin immunoreactivity in Ewing's sarcoma: prevalence in 50 cases confirmed by molecular diagnostic studies. Am J Surg Pathol 24(3):410–416
Collini P, Sampietro G, Bertulli R, Casali PG, Luksch R, Mezzelani A, Sozzi G, Pilotti S (2001) Cytokeratin immunoreactivity in 41 cases of ES/PNET confirmed by molecular diagnostic studies. Am J Surg Pathol 25(2):273–274
Schuetz AN, Rubin BP, Goldblum JR, Shehata B, Weiss SW, Liu W, Wick MR, Folpe AL (2005) Intercellular junctions in Ewing sarcoma/primitive neuroectodermal tumor: additional evidence of epithelial differentiation. Mod Pathol 18(11):1403–1410
Srivastava A, Rosenberg AE, Selig M, Rubin BP, Nielsen GP (2005) Keratin positive Ewing's sarcoma: an ultrastructural study of 12 cases. Int J Surg Pathol 13(1):43–50
Machado I, Navarro S, López-Guerrero JA, Alberghini M, Picci P, Llombart-Bosch A (2011) Epithelial marker expression does not rule out a diagnosis of Ewing's sarcoma family of tumours. Virchows Arch 459(4):409–414
López-Guerrero JA, Machado I, Scotlandi K, Noguera R, Pellín A, Navarro S, Serra M, Calabuig-Fariñas S, Picci P, Llombart-Bosch A (2011) Clinicopathological significance of cell cycle regulation markers in a large series of genetically confirmed Ewing's sarcoma family of tumors. Int J Cancer 128(5):1139–1150
Llombart-Bosch A, Machado I, Navarro S, Bertoni F, Bacchini P, Alberghini M, Karzeladze A, Savelov N, Petrov S, Alvarado-Cabrero I, Mihaila D, Terrier P, Lopez-Guerrero JA, Picci P (2009) Histological heterogeneity of Ewing's sarcoma/PNET: an immunohistochemical analysis of 415 genetically confirmed cases with clinical support. Virchows Arch 455(5):397–411
Kavalar R, Pohar Marinsek Z, Jereb B, Cagran B, Golouh R (2009) Prognostic value of immunohistochemistry in the Ewing's sarcoma family of tumors. Med Sci Monit 15(8):CR442–CR452
Makino T, Yamasaki M, Takeno A, Shirakawa M, Miyata H, Takiguchi S, Nakajima K, Fujiwara Y, Nishida T, Matsuura N, Mori M, Doki Y (2009) Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell carcinoma of the oesophagus. Br J Cancer 101(8):1298–1306
Papagerakis S, Shabana AH, Pollock BH, Papagerakis P, Depondt J, Berdal A (2009) Altered desmoplakin expression at transcriptional and protein levels provides prognostic information in human oropharyngeal cancer. Hum Pathol 40(9):1320–1329
Subramaniam MM, Navarro S, Llombart-Bosch A (2011) Immunohistochemical study of correlation between histologic subtype and expression of epithelial-mesenchymal transition-related proteins in synovial sarcomas. Arch Pathol Lab Med 135(8):1001–1009
He H, Chen W, Wang X, Wang C, Liu F, Shen Z, Xu J, Gu J, Sun Y (2012) Snail is an independent prognostic predictor for progression and patient survival of gastric cancer. Cancer Sci. doi:10.1111/j.1349-7006.2012.02295.x
Sharili AS, Allen S, Smith K, Hargreaves J, Price J, McGonnell I (2011) Expression of Snail2 in long bone osteosarcomas correlates with tumour malignancy. Tumour Biol 32(3):515–526
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This study was supported by prognostic and therapeutic targets in the Ewing's family of tumors, contract 503036, and EuroBoNet, European network to promote research into uncommon cancers in adults and children, contract 018814.
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The authors wish to dedicate this article to the memory of Prof. Marco Alberghini who sadly passed away while this paper was in press.
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Machado, I., López-Guerrero, J.A., Navarro, S. et al. Epithelial cell adhesion molecules and epithelial mesenchymal transition (EMT) markers in Ewing's sarcoma family of tumors (ESFTs). Do they offer any prognostic significance?. Virchows Arch 461, 333–337 (2012). https://doi.org/10.1007/s00428-012-1288-x
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DOI: https://doi.org/10.1007/s00428-012-1288-x