Epithelial cell adhesion molecules and epithelial mesenchymal transition (EMT) markers in Ewing's sarcoma family of tumors (ESFTs). Do they offer any prognostic significance?
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.
Pathology Department, Instituto Valenciano de Oncología, Valencia, Spain.
Isidro
I
Machado
José A
JA
López-Guerrero
Samuel
S
Navarro
Marco
M
Alberghini
Katia
K
Scotlandi
Piero
P
Picci
Antonio
A
Llombart-Bosch
D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001859:Bone Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D051180:Desmoplakins / Q000378:metabolism; D018572:Disease-Free Survival; D000071858:Epithelial Cell Adhesion Molecule; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D011379:Prognosis; D012512:Sarcoma, Ewing / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D013030:Spain / Q000453:epidemiology; D015996:Survival Rate
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D051180:Desmoplakins; D000071858:Epithelial Cell Adhesion Molecule; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3