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.
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.
Mazumdar
Madhu
M
Memorial Sloan-Kettering Cancer Center, 307 E 63rd St, 3rd Floor, New York, NY 10021, USA. mazumdar@biost.mskcc.org.
Bacik
Jennifer
J
Tickoo
Satish K
SK
Dobrzynski
Deborah
D
Donadio
Alessia
A
Bajorin
Dean
D
Motzer
Robert
R
Reuter
Victor
V
Bosl
George J
GJ
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*
D014408:Biomarkers, Tumor; D006063:Chorionic Gonadotropin; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D000509:alpha-Fetoproteins