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/

Histopathologic features alone fail to reliably stratify patients with clinical Stage A nonseminomatous germ cell tumors of the testis into groups with high and low risk for occult metastatic disease. Previous Bow cytometric studies at Indiana University demonstrated a significan t correlation between high proliferative activity and metastatic disea se. The current study evaluated the prognostic significance of immunoh istochemical markers related to tumor proliferation and aggressiveness in a consecutive series of clinical Stage A nonseminomatous germ cell tumors patients who underwent retroperitoneal lymph node dissection. Archival material of the orchiectomy specimens of 62 patients (45 path ologic Stage A, 17 with metastatic disease) was reviewed and immunohis tochemically stained for Ki-67 antigen (MIB-1), proliferation-associat ed nuclear antigen (PC10), p53 protein (Pab1801), and Factor-VIII-rela ted antigen (neovascularization). Staining with MIB-1 was significantl y higher in the metastatic group (mean 80.2%, standard deviation [SD] 15.5) than in pathologic Stage A cases (66.3%, SD 27.9; P = 0.0032) an d was predictive of metastatic status with a sensitivity of 82% and sp ecificity of 69%. In this study, no patient with a MIB-1 value less th an 52% had metastases. Proliferation-associated nuclear antigen and p5 3 staining correlated with MIB-1 values (R = 0.63 and 0.55, respective ly) but did not correlate with metastatic status. Tumor angiogenesis w as also not predictive of metastatic status. Assessment of proliferati on rates using MIB-1 antibody in clinical Stage A nonseminomatous germ -cell-tumor patients may prove helpful in predicting metastatic status . A subgroup of patients with very low proliferation rates may especia lly benefit from MIB-1 analysis, because they were at very low risk fo r metastatic disease. Proliferation-associated nuclear antigen, p53 ex pression, and neovascularization were not able to discriminate between cases with and without metastases.