Estramustine-binding protein (EMBP) was determined immunohistochemically in prostatic cancer (PC) specimens taken from patients before and after therapy. The EMBP staining intensity was correlated with the tumor malignancy grade in untreated PCs. The effect of various treatments (i.e., androgen-withdrawal therapy, treatment with estramustine phosphate or radiation) on the expression of EMBP was also investigated. Although a rabbit polyclonal antiserum raised against rat EMBP was used all through the study, all untreated PCs (n = 53) examined so far displayed a positive immunoreaction. The staining intensity was higher in moderately and poorly differentiated than in well-differentiated tumors. Furthermore, two types of staining patterns were observed, that is, a diffuse type in about 70% and a focal in the remaining cases, which might reflect the multifocal appearance of PCs. The prognostic significance of these staining patterns is discussed. Irrespective of the treatment used, EMBP staining was reduced to lower or undetectable levels in PCs where cytological as well as clinical regression were indicated after 6-30 months of therapy. In nonresponders or patients with refractory disease, however, EMBP expression reappeared and returned to pretreatment levels. In a short-term follow-up, the diminuation of EMBP was evident as early as 10 days after androgen-withdrawal therapy and persisted as long as the patient responded to therapy. When estramustine phosphate was given as secondary treatment to hormone refractory PCs, EMBP decreased to undetectable levels in 3/4 of the specimens, suggesting response to therapy. In conclusion, a decreased EMBP staining was well correlated with favorable cytological regression as well as with clinical regression, whereas unchanged staining intensity was indicative of clinical progression and a poor cytological regression grade. The high levels of EMBP in moderately and poorly differentiated tumors as well as in relapsing PCs, despite continued androgen withdrawal, strongly support a regulation of EMBP that is not under androgenic control. Based on the present findings, we suggest the use of EMBP as a therapy marker. Provided that immunohistochemical measurements can be performed on fine-needle aspirates, EMBP analysis may be a direct and early means to distinguish between responding patients and nonresponders.

An animal model was established to test the effect of a calcium antagonist on nephrocalcinosis, which was induced by an atherogenous diet, and its effect on the excretion of calcium and other parameters relevant for stone formation. With the administration of nifedipine (Adalat®), the grade of nephrocalcinosis could be significantly reduced. Furthermore, with nifedipine the excretion of calcium and sodium in the urine was raised, while phosphate and potassium levels were lowered. The excretion of magnesium and citrate, reduced by an atherogenous diet, could be raised significantly with the administration of nifedipine. The pathophysiological mechanisms underlying the effect of nifedipine on nephrocalcinosis and on the excretion of the urine parameters are discussed. Apparently hypercalciuria is the result of a reduced reabsorption of calcium in the tubulus. The inhibitory effect on the genesis of nephrocalcinosis is possibly due to the lower calcium influx into the tubular cells.

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An immunohistochemical technique for determination of "estramustine-binding protein" (EMBP) in rat prostate is described. The localization and staining intensity of this protein were correlated to prostatic morphological structures in intact animals and at different time intervals after androgen deprivation by castration. EMBP was found almost exclusively in epithelial cells, while the fibromuscular stroma seemed to be negative. Intracellularly, immunostaining was confined to the cytoplasm, but was absent in nuclei. In intact rats, acinar lumina demonstrated heavy immunostaining, indicating secretion of EMBP. Orchiectomy caused a diminution of EMBP expression as well as secretion, suggesting that EMBP synthesis is under androgenic regulation. Human benign hyperplastic and cancerous prostatic specimens were also examined. All human specimens examined so far exhibited positive epithelial staining although of varying intensity. Therefore, this immunohistochemical technique may be used for studying the correlation of EMBP with tumor malignancy grade and for clinical investigations of how various treatments affect EMBP expression in prostatic carcinomas.

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