title: Persistent CD30 expression by embryonal carcinoma in the treatment time course: prognostic significance of a worthwhile target for personalized treatment.
abstract: OBJECTIVE
  CD30 is expressed by untreated embryonal carcinoma, supporting the rationale for a targeted approach. However, the reported chemotherapy induced switching off of CD30 noted on immunohistochemistry may affect its therapeutic potential for disease relapse. We evaluated persistent CD30 expression and its prognostic meaning in cases of post-chemotherapy residual disease.
  
  
  METHODS
  Paraffin blocks of surgical samples that yielded nonteratomatous viable cells after 1 or more cisplatin based chemotherapy treatments were retrieved and reassessed by 2 pathologists blinded to the study purpose. Multivariable analysis was done for prespecified factors.
  
  
  RESULTS
  A total of 49 cases of pure embryonal carcinoma or mixed germ cell tumor from August 1991 to August 2012 had full clinical data and suitable tissue available for analysis. Of the 35 cases (71.4%, 95% CI 56.7-83.4) with preserved CD30 positivity 14 (40.0%) showed residual disease after a median of 1 regimen (IQR 1-2). Five-year overall survival in CD30 positive and negative cases was 37.0% (95% CI 22.1-61.8) and 50.1% (95% CI 27.9-90.0, p=0.078), while after first line treatment it was 23.2% (95% CI 8.6-62.5) and 47.6% (95% CI 18.8-100, p=0.025), respectively. On multivariable analysis CD30 positivity was a significant prognostic factor for progression-free survival (HR 2.32, 95% CI 1.04-5.19) and overall survival (HR 2.77, 95% CI 1.05-7.29).
  
  
  CONCLUSIONS
  CD30 was retained even after an intensive pretreatment load, confirming that it is a reliable treatment target. Its expression was associated with a significantly poorer prognosis in multiple relapse/chemoresistant cases and it was an independent prognostic factor for survival.
authors.affiliation: Department of Medical Oncology, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Giannatempo
authors.forename: Biagio
authors.initials: B
authors.lastname: Paolini
authors.forename: Rosalba
authors.initials: R
authors.lastname: Miceli
authors.forename: Daniele
authors.initials: D
authors.lastname: Raggi
authors.forename: Nicola
authors.initials: N
authors.lastname: Nicolai
authors.forename: Elena
authors.initials: E
authors.lastname: Farè
authors.forename: Mario
authors.initials: M
authors.lastname: Catanzaro
authors.forename: Davide
authors.initials: D
authors.lastname: Biasoni
authors.forename: Tullio
authors.initials: T
authors.lastname: Torelli
authors.forename: Silvia
authors.initials: S
authors.lastname: Stagni
authors.forename: Luigi
authors.initials: L
authors.lastname: Piva
authors.forename: Luigi
authors.initials: L
authors.lastname: Mariani
authors.forename: Roberto
authors.initials: R
authors.lastname: Salvioni
authors.forename: Maurizio
authors.initials: M
authors.lastname: Colecchia
authors.forename: Alessandro Massimo
authors.initials: AM
authors.lastname: Gianni
authors.forename: Andrea
authors.initials: A
authors.lastname: Necchi
mesh_terms: D018236:Carcinoma, Embryonal / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D017730:Ki-1 Antigen / Q000096:biosynthesis*; D008297:Male; D018365:Neoplasm, Residual; D057285:Precision Medicine; D011379:Prognosis; D012189:Retrospective Studies; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D017730:Ki-1 Antigen
keywords: AFP; CD30; ECA; GCT; HCG; MVA; OS; PFS; antigens; carcinoma; drug resistance; embryonal; embryonal carcinoma; germ cell tumor; human chorionic gonadotropin; multivariable analysis; overall survival; progression-free survival; recurrence; testis; α-fetoprotein