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Background: Clinical studies have shown that a marked lymphoplasmocytic reaction in breast tumors s associated with poor prognosis. Such findings raise the possibility that an inflammatory cell reaction might be a tumor-induced response that tends to promote tumor growth. Purpose: We assessed the expressed of colony-stimulating factor-1 (CSF-1) as well as the prevalence of specific tumor-infiltrating lymphocytes and monocytes in breast tumors. Methods: Tissue sections were obtained from archival paraffin blocks from 196 breast cancer patients. Seventy-eight percent of the women had been treated by mastectomy and 22% by lumpectomy. Median age of the patients was 54 years, and median follow-up was 7.3 years. Immuno-histochemical and in situ hybridization techniques were used to characterize the specimens. Results: Markedly high numbers of CD45RO-positive T- and L26-positive B-cell infiltrates were found in 13% and 17% of the tissue specimens, respectively. CSF-1 receptor-positive monocytes were detected in 48% and CD68-positive monocytes in 90% of the tumors. In turn, tumors with large fractions of CD68-positive monocytes also showed CSF-1 receptor-positive monocytes (P

An enzyme-linked immunosorbent assay using monoclonal and polyclonal antibodies against recombinant pS2 was devised. It was used to measure pS2 concentration in the cytosol of 339 breast cancers, 15 fibroadenomas, 16 cases of benign breast disease, and 6 normal breast tissues. The mean value of pS2 concentration was higher in cancer, but the protein could be detected readily in benign tumors and even in normal breast. The concentration of pS2 was significantly lower in postmenopausal women and tumors of differentiation Grade 3. The pS2 concentration was correlated strongly with the presence of estrogen receptors (ER) and progesterone receptors (PR). No correlation was observed with the size, histologic type of the tumor, and lymph node status. The prognostic value of pS2 appeared relatively limited. It was clear cut only for a relatively small group of patients ( 15%), who had low concentrations of pS2 ([is less than or equal to] 0.32 ng/mg of protein). These patients had a shorter disease-free interval and overall survival time. The most striking correlation was observed with the outcome of adjuvant hormone therapy. pS2 concentration was shown to be the most potent prognostic factor, preceding even ER. Cancer 1992; 69:2116-2123.

Introduction: Prognostic factors can be useful to identify node-negative patients at increased risk of relapse who should receive adjuvant treatment. In the past, oestrogen receptor status and mitotic index have been shown to be significant predictors of prognosis. Different techniques for the measurement of these prognostic factors are available. Methods: Paraffin-embedded tumour specimens from 441 pre-menopausal patients with node-negative breast cancer who were previously randomized onto a trial comparing peri-operative chemotherapy with no further therapy were studied. Oestrogen receptor status was determined by the classical biochemical assay and by immunohistochemistry (ER-IA). Mitotic index was assessed by counting the number of mitoses and by calculating the percentage of tumour cells positively staining for the antibody Ki-67. Results: There was a good correlation between ER-IA and the biochemical ER-assay (P<0.01), and the percentage of Ki-67 positive tumour cells and mitotic counts (P<0.01) respectively. However, ER-IA significantly predicted disease-free survival (RR=2.67, 95% CI: 1.60–4.44, P<0.01) whereas the biochemical assay was only borderline significant (RR=1.54, 95% CI: 1.00–2.36, P=0.05). Similarly, Ki-67 was a stronger indicator of prognosis (RR=2.84, 95% CI: 1.80–4.48, P<0.01) than mitotic counts (RR=1.56, 95% CI: 1.22–2.00, P<0.01). Conclusions: We conclude that ER-IA performs better in predicting prognosis than the classical biochemical oestrogen receptor assay. Ki-67 is a more accurate marker for tumour cell proliferation and predicts prognosis of patients with breast cancer better than do mitotic counts. Copyright 1999 W.B. Saunders Company Ltd

A radioimmunoassay method to measure progesterone receptor in rabbit and human tissues was devised and applied to human breast cancer. A specific progesterone receptor antibody was prepared by purifying rabbit receptor by immunoaffinity chromatography, sodium dodecylsulphate-polyacrylamide gel electrophoresis and injection of the isolated 110 000 dalton receptor band into a goat. Immunoblot studies of progesterone target and non-target tissues showed the specificity of the antibody, which was used at a dilution of 1/45 000. The tracer consisted of 125I-labelled electroeluted 110 000 dalton receptor.The sensitivity of the method was 1 fmol/tube for the rabbit receptor and 3 fmol/tube for the human receptor. The intra-assay coefficient of variation was 11% for tumours positive for the progesterone receptor and 9·9% for those on the borderline (10–30 fmol receptor/mg protein). The interassay coefficients of variation were 20 and 19% respectively. The correlation between the radioimmunoassay and a steroid-binding assay was studied in 40 tumour biopsies. In 39 cases, very good correlation was found (r= 0·99); in a single case an immunoreactive protein was detected which apparently bound steroid poorly.One important feature of this method was that receptor immunoreactivity remained unchanged when either the tissue or the cytosol was exposed to a temperature of 20 °C for relatively long periods of time. Under the same conditions the steroid-binding capacity declined rapidly. This characteristic of the radioimmunoassay may prevent errors due to improper handling of tissue samples. Such stability was not observed for oestrogen receptors when measured by a sandwich immunoenzymatic method after incubation of tissue at 20 °C.J. Endocr.(1988) 116,427–434