title: Cluster analysis of p53 and Ki67 expression, apoptosis, alpha-fetoprotein, and human chorionic gonadotrophin indicates a favorable prognostic subgroup within the embryonal carcinoma germ cell tumor.
abstract: OBJECTIVE
  The prognostic information provided by alpha-fetoprotein and human chorionic gonadotrophin in the management of germ cell tumor (GCT) patients is a biochemical reflection of tumor differentiation. Ki67, p53, and apoptosis have been found to be related to proliferation (Ki67), cell death (p53, apoptosis), and possibly differentiation chemoresistance (p53). We sought to determine whether simultaneous expression of one or more of these markers could identify clinically relevant subgroups of patients with nonseminomatous GCT (NSGCT).
  
  
  METHODS
  These five marker values were obtained for 95 previously untreated patients with embryonal carcinoma with or without other germ cell components. A multivariate cluster analysis was performed to identify patients with similar marker patterns.
  
  
  RESULTS
  One prominent cluster (n = 37; 36 testis retroperitoneum), consisting of 26 (70%) good-risk (GR), nine (24%) intermediate-risk (IR), and two (6%) poor-risk (PR) patients, as defined by the International Germ Cell Consensus Cancer Group (IGCCCG), was observed. The 5-year survival of the prominent cluster (with 30% IR/PR patients) was 94% (95% confidence interval [CI], 86% to 100%), which is comparable to the 91% (95% CI, 89% to 93%) 5-year survival of the IGCCCG GR patients. IGCCCG risk status (P =.005) and cluster affiliation (P =.04) were independent predictors of outcome with hazard ratios of 5.0 (95% CI, 1.6 to 15.4) and 4.6 (95% CI, 1.04 to 20.1), respectively.
  
  
  CONCLUSIONS
  These results suggest that there is a subgroup of NSGCT patients with embryonal carcinoma (with or without other histologies) with a specific tumor biology profile (high Ki67, low apoptosis, and low p53) whose survival is better than that of the overall patient group. The unexpectedly good outcome for the prominent cluster and independent-risk status suggest that subgroups of GCT reflecting different abilities to respond to treatment exist within IGCCCG prognostic categories.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, 307 E 63rd St, 3rd Floor, New York, NY 10021, USA. mazumdar@biost.mskcc.org.
authors.forename: Madhu
authors.initials: M
authors.lastname: Mazumdar
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bacik
authors.forename: Satish K
authors.initials: SK
authors.lastname: Tickoo
authors.forename: Deborah
authors.initials: D
authors.lastname: Dobrzynski
authors.forename: Alessia
authors.initials: A
authors.lastname: Donadio
authors.forename: Dean
authors.initials: D
authors.lastname: Bajorin
authors.forename: Robert
authors.initials: R
authors.lastname: Motzer
authors.forename: Victor
authors.initials: V
authors.lastname: Reuter
authors.forename: George J
authors.initials: GJ
authors.lastname: Bosl
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D006063:Chorionic Gonadotropin / Q000032:analysis*; D016000:Cluster Analysis; D015331:Cohort Studies; D015972:Gene Expression Regulation, Neoplastic; D018237:Germinoma / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000032:analysis* / Q000235:genetics; D008297:Male; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D018239:Seminoma / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D013736:Testicular Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics; D000509:alpha-Fetoproteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D006063:Chorionic Gonadotropin; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D000509:alpha-Fetoproteins