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Biomedical subjects

D C Allred

Publications and source records attributed to D C Allred.

77 records · Page 5Linked to original sources

Immunocytochemical analysis of estrogen receptors in human breast carcinomas. Evaluation of 130 cases and review of the literature regarding concordance with biochemical assay and clinical relevance.

An estrogen receptor-immunocytochemical assay (ER-ICA) was performed on frozen sections of 130 samples of human breast carcinoma. A standard dextran-coated charcoal assay (DCCA) was performed on the same samples. Concordance of results between the tests was 91%. The sensitivity and specificity of the ER-ICA, compared with the DCCA, were 92% and 89%, respectively. We describe the ER-ICA technique and review the literature regarding the use of the ER-ICA in evaluating breast cancer with respect to the agreement of results with the DCCA, the nature of discordant results, the ability to predict the clinical response to hormone therapy, and the ability to predict disease-free survival. The combined experience of many studies has shown that the ER-ICA is a highly specific and sensitive method for measuring the level of ERs in breast tumors with a high level of agreement with the DCCA. Early experience has suggested that the ER-ICA can predict the response to hormone therapy and disease-free survival, as well as or better than the DCCA. The evaluation of receptor heterogeneity, made possible by the ER-ICA, may enhance our ability to discriminate ER-positive tumors with a relatively high risk of recurrence.

Breast Neoplasms↗

Anaplastic large cell (Ki-1) lymphoma with histiocytic phenotype simulating carcinoma.

Histiocytic and epithelial cell types share many cytomorphologic and functional characteristics; it is predictable, therefore, that corresponding malignancies might be difficult to distinguish. Described is the case of a 52-year-old woman in whom disseminated anaplastic large-cell lymphoma simulated carcinomatosis by conventional morphologic criteria. Evidence of histiocytic differentiation was derived from immunocytochemical, fine structural, and genetic probe analyses. The diagnosis of histiocytic neoplasia is discussed in relation to categories previously termed malignant histiocytosis, "Ki-1" lymphoma, and regressing atypical histiocytosis, and comparisons are made with animal tumor models.

Antibodies, Monoclonal↗

Blockade of the type I somatomedin receptor inhibits growth of human breast cancer cells in athymic mice.

Insulin and insulin-like growth factors (IGIs) stimulate the growth of human breast cancer cells in vitro. The type I somatomedin receptor (SR) expressed in these cells may mediate the growth effects of these peptides. We have examined the role of this receptor on human breast cancer growth with a monoclonal antibody (alpha-IR-3) that blocks the receptor binding domain and inhibits IGF-I-induced growth. alpha-IR-3 inhibited clonal growth in vitro and blocked the mitogenic effect of exogenous IGF-I in both MCF-7 and MDA-231 breast cancer cell lines. Antibody-induced blockade of the type I SR also inhibited the estrogen-independent MDA-231 cells growing in vivo in nude mice, but growth of the estrogen-dependent MCF-7 cells was unaffected. IGIs are important growth regulators of MDA-231 breast cancer cells. Blockade of this growth stimulatory pathway may provide a new treatment strategy.

Animals↗

Anergy-like immunosuppression in mice bearing pulmonary foreign-body granulomatous inflammation.

Pulmonary granulomas were induced in BALB/c mice by the intratracheal injection of insoluble polymerized dextran and latex microparticles. Very large granulomas developed around dextran beads, which reached peak intensity within 2-3 days and rapidly declined in size thereafter. Latex beads generated small stable lesions. The involvement of cell-mediated immunity could not be demonstrated in the inflammatory responses induced by either type of bead. Antigen-induced delayed type hypersensitivity (DTH) and mitogen-induced DTH-like footpad reactions were markedly suppressed in immunized mice bearing early dextran granulomas. Mitogen-induced DTH-like footpad reactions were suppressed in unimmunized animals bearing early dextran foreign-body granulomas. Antigen- and mitogen-induced footpad swelling recovered to normal levels as dextran granulomas diminished in size. No suppression of these footpad reactions was observed in mice bearing small latex foreign-body granulomas. The intraperitoneal injection of aqueous extracts prepared from the lungs of unimmunized donor animals bearing early dextran foreign-body granulomas could partially transfer suppression of mitogen DTH-like footpad responses to normal mice. These results suggest that cells within large, nonimmunologic lung granulomas produce a soluble factor which participates in the expression of anergy-like immunosuppression.

Animals↗

Expression of HER-2/neu oncoprotein in human breast cancer: a comparison of immunohistochemical and western blot techniques.

Three hundred and one primary breast cancers from patients with tumor infiltrated lymph nodes were analyzed for the presence of HER-2/neu oncoprotein by two procedures: Western blot (WB) and immunohistochemistry (IHC). Overexpression of this protein was found by WB in 16.6% of the tumors, and by IHC in 16.3%. Concordance between the two methods was found in 95% of tumors (286/301). In 7 cases we found HER-2/neu by IHC but not by WB, while the opposite was found in the remaining 8 patients. This discrepancy was found mainly in samples with HER-2/neu values just above the cut points and were therefore close to the sensitivity limits of the procedures used here. This study helps to define the parameters that should be considered to evaluate the immunostaining for HER-2/neu as positive (i.e., membrane staining, IHC score of 2 or more). The results obtained by both techniques were correlated with several currently used prognostic factors. Higher HER-2/neu protein expression was found in tumors lacking estrogen or progesterone receptors, in tumors with high S-phase fraction and in patients with more than 3 positive lymph nodes. In contrast, no relationship was found between overexpression of this protein and tumor size, ploidy, or age of the patient. Patients with elevated HER-2/neu expression showed a significantly worse overall survival by both methods, IHC (p = 0.05) and WB (p = 0.001). In conclusion, there is very high agreement between IHC and WB when measuring expression of HER-2/neu and both techniques showed prognostic significance.

Biomarkers, Tumor↗