PROGNOSTIC MARKERS IN PHEOCHROMOCYTOMA

Clinical and histopathological features do not reliably distinguish be tween benign and malignant pheochromocytomas. Additional markers that might be useful prognostic indicators in the pathological assessment o f these tumors are sought. Immunohistochemical expression of MIB-1, Bc l-2, cathepsin B, cathepsin D, basic fibroblast growth factor (bFGF), c-met, and type TV collagenase were studied on formalin-fixed tissue f rom 33 nonconsecutive cases of pheochromocytoma, selected on the basis of reliable long-term follow-up, to determine associations with malig nancy. The study group included 33 patients, 19 men and 14 women, with a mean age of 45 years, including live cases of neurofibromatosis (NF ), three familial, and one MEN IIb. Mean follow-up was 63.2 months. Te n patients were determined to have malignant pheochromocytomas br the presence of metastatic disease. Features found to be associated with m alignancy included MIB-1 labeling index (5% vs 1%) (P = .0009), male g ender (90% vs 43%) (P = .008), extra-adrenal location (40% vs 9%) (P = .03), tumor weight (481 g vs 124 g) (P = .05), and young age (38 year s vs 49 years) (P = .05). None of the five cases with NF tvere maligna nt (P = .04). S-100 positivity showed a significant (P = .02) but nonl inear association with benign tumors. Absent S-100 correlated with gre ater tamer weight. Malignancy was not associated with right versus lef t side or bilaterality, although bilateral tumors-ic-ere smaller. C-me t bFGF, cathepsin B, cathepsin D, and collagenase were strongly expres sed in most tumors and were not predictive of outcome, nor was bcl-2, which was variably expressed. Using multiple logistic regression with malignancy as the dependent variable, MIB-1 continued to show a signif icant association with malignancy (P = .005) independent of any associ ation with sex, age, or extra-adrenal location. Using a cutoff value o f MIB-1 labeling of greater than 3% yielded a specificity of 100% and a sensitivity of 50% in predicting malignancy. Copyright (C) 1998 by W .B. Saunders Company.