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 Journal Article

Authors: Mazumdar, M.; Bacik, J.; Tickoo, S. K.; Dobrzynski, D.; Donadio, A.; Bajorin, D.; Motzer, R.; Reuter, V.; Bosl, G. J.
Article 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: Purpose: 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). Patients and 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. Conclusion: These results suggest that there is a sub-group 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. © 2003 by American Society of Clinical Oncology.
Keywords: immunohistochemistry; survival; controlled study; protein expression; survival analysis; retrospective studies; major clinical study; genetics; histopathology; comparative study; cancer staging; neoplasm staging; sensitivity and specificity; ki 67 antigen; ki-67 antigen; cytology; apoptosis; cohort studies; cluster analysis; gene expression; tumor markers, biological; cohort analysis; cell differentiation; pathology; retrospective study; protein p53; tumor marker; physiology; gene expression regulation; gene expression regulation, neoplastic; biopsy, needle; needle biopsy; testis tumor; testicular neoplasms; prediction and forecasting; predictive value of tests; tumor suppressor protein p53; multivariate analysis; cancer classification; nick end labeling; germ cell tumor; testis; embryonal carcinoma; seminoma; retroperitoneum; alpha fetoprotein; chorionic gonadotropin; in situ nick-end labeling; germinoma; alpha-fetoproteins; humans; prognosis; human; male; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 21
Issue: 14
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2003-07-15
Start Page: 2679
End Page: 2688
Language: English
DOI: 10.1200/jco.2003.03.136
PUBMED: 12860944
PROVIDER: scopus
Notes: Export Date: 12 September 2014 -- Source: Scopus
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MSK Authors
  1. Dean Bajorin
    402 Bajorin
  2. Robert Motzer
    742 Motzer
  3. Madhu Mazumdar
    120 Mazumdar
  4. Satish K Tickoo
    369 Tickoo
  5. Victor Reuter
    898 Reuter
  6. George Bosl
    255 Bosl
  7. Jennifer M Bacik
    46 Bacik