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The prognostic significance of the lysosomal protease cathepsin D in breast cancer was evaluated in a retrospective study. Cathepsin D was measured in 346 deep-frozen (-70 degrees C) cytosol specimens of primary breast carcinomas (1982-1990). Among the established prognostic factors, only axillary lymph node involvement correlated with the expression of cathepsin D (> 40/60 pmol/mg) (p = 0.04-0.05). Univariate analyses of disease-free survival (DFS) and overall survival (OS) showed, that the expression of cathepsin D had no effect on the prognosis either in the whole population of breast cancer patients during long-term follow-up (n = 302; median observation time 51 months) or in the group of women with positive lymph nodes (n = 157; 46 months). However, within the group of N0 patients (n = 145; 57 months), high cathepsin D levels were associated with an unfavourable OS, but this relationship was statistically insignificant (p = 0.08-0.13). A similar influence of cathepsin D on DFS could not be demonstrated. Compared to tumour size, grading and receptor status in multivariate analysis, cathepsin D was a more indicative, but finally insignificant prognostic factor for OS. According to these results, cathepsin D may contribute only in combination with other prognostic factors to identify those 20-30% of node-negative patients with unfavourable prognosis, who may benefit from adjuvant therapy.

The pathogenesis of shock is discussed on the basis of important results from world literature under the special point of view of the significance of eicosanoids. It results from a lower mortality of shock animals with a diet poor in polyunsaturated fatty acids and a specifically increased release of arachidonic acid as prostaglandin precursor in shock animals. Of particular importance is an increased formation of thromboxane B2 (TXB2). It this formation is specifically inhibited, the survival rate increases, the decrease of blood pressure is reduced, also the increase of the plasma-cathepsin-D-activity and of the myocardial depressant factor and the increased formation of microthrombi in renal glomeruli of shock animals. Also in patients who survived the shock the TXB2-values were only 1/10 of the values in decreased shock patients. Another therapeutic way is the infusion of prostacyclin which leads to a specific increase of the arterial blood supply of the liver and the superior mesenteric artery and also increases the ATP and creatine phosphate level. The importance of the findings of animal experiments for the pathogenesis and therapy in patients is discussed.

Cathepsin D in serum of women in labour, retroplacental blood and newborn's blood degradate hemoglobine denatured with urea and the serum protein most intensively in pH 3,5. The denatured protein is more liable to cathepsin D activity than the serum protein. Cathepsin D of the retroplacental blood serum shows the highest activity, the activity in the blood serum of women in labour is lower and it is the lowest in the newborn's blood.