Prostaglandins (PGs), especially of the E-series, have been shown to be elevated in a large number of human and experimental tumours. Special efforts have been made to investigate the features and the role of PG-synthesis in human breast cancer (Bennett et al., 1975;Powles et al., 1976; Kibbey et al., 1980;Greaves et al., 1980;Malachi et al., 1981;Campbell et al., 1983).A considerable volume of research on the mechanisms of action of PGs in a wide variety of cells and tissues, indicates that PGs are possibly involved in tumour initiation, tumour promotion, cell proliferation and differentiation, the immune response, tumour metastasis, osteolysis and hypercalcaemia (Karmali, 1980;Honn et al., 1981a;Droller, 1981;Goodwin, 1981).The present study was designed to describe the basic features of PGF2X, production in benign and malignant breast tumours. Normal glandular breast tissues were used as controls. We determined PGF2<,, because this product is more stable than Brune et al., 1978). Therefore the numbers of host-derived cells and the amount of necrosis were evaluated by means of quantitative microscopy. The epithelial cellularity was also evaluated by morphometric determination of the mean nuclear density and mean nuclear area. Materials and methodsThere were 165 specimens from 106 patients who underwent surgery for a breast lump. Each C) The Macmillan Press Ltd., 1985
Summary 6-keto-PGFi,, and thromboxane B2 were determined by radioimmunoassay in 37 extracts of breast carcinomata, 8 fibroadenomata, 12 sclerocystic-disease specimens and 51 normal breast tissues. More prostanoids were extracted from carcinomata than from normal specimens, fibroadenomata or sclerocysticdisease tissues (P<0.05). The 6-keto-PGF1./TXB2 ratio was higher in carcinomata than in normal tissues and fibroadenomata (P<0.05) but was not significantly different from the ratio in sclerocystic disease. The prostaglandin levels and the 6-keto-PGF1./TXB2 ratios from carcinomata did not correlate significantly with age, tumour size, differentiation, lymph node status, nuclear-cytoplasmic ratio, host cell reaction, mast cells, necrosis, elastosis, fibrosis or blood vessel density. Lower nuclear density was associated with lower 6-keto-PGF1,/TXB2 ratios (P=0.01) whereas the latter value was higher when infiltration was lower (P=0.03). There was a positive correlation between mitotic index and the 6-keto-PGF1./TXB2 ratio (P=0.04).Cumulation of variables revealed lower prostanoid ratios in tumours >2cm without lymph node metastasis then tumours <2cm with lymph node metastasis (P=0.05). A first follow-up (14 months) showed a higher 6-keto-PGF1./TXB2 ratio in patients who developed metastasis (P=0.04). Our study does not confirm the hypothesis that high prostacyclin levels are a good prognostic index in breast cancer.Honn et al. (1981) found that prostacyclin (PGI2) had a beneficial influence against metastasis of B16 amelanotic melanoma tumours in mice, whereas inhibitors of PGI2 synthesis enhanced the number of metastases. Other authors tested the antimetastatic potency of acetylsalicylic acid, indomethacin, dipyridamole, flurbiprofen, benorylate, heparin and warfarin (Gasic et al., 1973;Elias et al., 1973;Lione & Bosman, 1978;Bennett, 1982). Most of these studies are done on animals and showed no clearcut results.Thromboxane (TX) A2 is often a physiological antagonist of PGI2 and an imbalance between them can disturb the (anti)haemostatic system. The antiaggregating properties of nonsteroidal antiinflammatory drugs (NSAID) can be explained by a stronger inhibition of the platelet cyclo-oxygenase in comparison with that of the vessel wall. As a result the release of TX will be lowered and aggregation will be blocked (Bunting et al., 1983). Sloane et al. (1981) showed that some tumours are able to release cathepsin B. This enzyme stimulates the synthesis of TX and is produced in a variant of B16 melanoma which has high metastatic activity.In order to study a possible prognostic value of the PGI2/TX ratio in breast cancer, the stable hydrolysis products of PGI2 (6-keto-PGF1,) and TXA2 (TXB2) were determined by RIA. 6-keto-PGF1, and TXB2 levels were examined in relation to the size of the tumour, axillary lymph node status, lymphatic vessel permeation, differentiation of the tumour, mitotic index density of nuclei of tumour cells, and age of the patient.PG production can be influenced by inflammatory processes (Humes...
In this prospective follow-up study the prognostic value of the tumor prostacyclin/thromboxane ratio in human breast carcinoma was investigated. The stable degradation products of prostacyclin and thromboxane (6-keto-PGF1α and TXB2, respectively), were measured by radio-immunoassay in homogenized primary tumours from 29 patients with primary non-metastatic breast cancer. The median follow-up was 43 months (range 24–58 months). Patients with recurrent disease or patients who died of breast cancer had a significantly higher 6-keto-PGF1α/TXB2 ratio than the disease-free survivors (p = 0.018 and p = 0.047, respectively). There was no significant difference in the 6-keto-PGF1α and TXB2 levels. These data indicate that the prostacyclin/thromboxane balance in the tumour might be a prognostic factor in breast cancer. Prostanoids may contribute to metastasis in breast cancer, but the problem is complex because the different prostaglandins have numerous actions that may produce both undesirable and desirable effects.
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