Affiliation:
1. From the Department of Epidemiology and Biostatistics, the Genitourinary Oncology Service, Division of Solid Tumor Oncology, and Department of Pathology, Memorial Sloan-Kettering Cancer Center; and Departments of Medicine and Pathology, Weill Medical College, Cornell University, New York, NY.
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 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.
Publisher
American Society of Clinical Oncology (ASCO)
Reference44 articles.
1. Testicular Germ-Cell Cancer
2. International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group.
3. Albers P, Orazi A, Ulbright TM, et al: Prognostic significance of immunohistochemical proliferation markers (Ki-67/MIB-1 and proliferation-associated nuclear antigen), p53 protein accumulation, and neovascularization in clinical stage A nonseminomatous testicular germ cell tumors. Mod Pathol 8:492,1995–497,
4. Knudson CM, Johnson GM, Lin Y, et al: Bax accelerates tumorigenesis in p53-deficient mice. Cancer Res 61:659,2001–665,
5. Lutzker SG: P53 tumour suppressor gene and germ cell neoplasia. APMIS 106:85,1998–89,
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