Search

Sastre-Garau X, Genin P, Rousseau A, Al Ghuzlan A, Nicolas A, Fréneaux P, Rosty C, Sigal-Zafrani B, Couturier J, Thiery J-P, Magdelénat H & Vincent-Salomon A (2004) Histopathology 45, 142–147 Increased cell size and Akt activation in HER-2/ neu-overexpressing invasive ductal carcinoma of the breast To determine whether cell size is related to HER-2/ neu status and/or to Akt activation in breast carcinomas. HER-2/ neu overexpression is observed in 20–30% of invasive breast carcinomas with poor pronostic features, but little is known about the cell phenotype associated with HER-2/ neu activation. Akt has been found to be involved in the HER-2/ neu signal transduction pathway and Akt activation has been associated with increased cell size in various models. A case–control study of invasive ductal carcinoma of the breast was carried out, including 21 cases displaying HER-2/ neu overexpression and 20 HER-2/ neu negative controls. Cytoplasmic and nuclear sizes were measured on digitized histological pictures using cell image analysis software. Akt expression analysis was performed by immunohistochemistry on formalin-fixed histological sections using an anti-phosphorylated-Akt (Ser473) antibody. HER-2/ neu-overexpressing carcinomas had a mean nuclear size of 75 ± 22.2 µm2 and a mean cytoplasmic size of 187 ± 52.3 µm2. Both values were higher than the nuclear and cytoplasmic size of HER-2/ neu-negative cases (nucleus = 58 ± 24.5 µm2, cytoplasm = 133 ± 56.6 µm2; P = 0.02 and P =0.003, respectively). Up to 75% of the tumours with a cell size over 140 µm2 were HER-2/ neu-positive. Immunohistochemical Akt expression was observed in 19/40 (47.5%) cases. The immunoreactivity was localized in the cytoplasm in eight cases, on the cell membrane in four cases and at both sites in seven cases. One case was not interpretable. Comparison between HER-2/ neu and Akt status showed that Akt was detectable at the cell membrane in 43% (9/21) of HER-2/ neu-positive and in 10% (2/19) of HER-2/ neu-negative cases ( P = 0.02). HER-2/ neu overexpression was consistently associated with increased cell size in invasive ductal carcinoma of the breast. This increase may be related to concomitant Akt activation. The assessment of activated pathways in HER-2/ neu-overexpressing breast carcinomas may provide useful information for optimized individual HER-2/ neu-targeted therapy. [ABSTRACT FROM AUTHOR]

That most cytotoxic agents act specifically against actively proliferating cells is well-recognized. In this study, we attempted to correlate pretreatment S-phase fractions (SPF) measured on DNA histograms with regression of the tumor mass after the administration of neoadjuvant chemotherapy. Tumor cells were obtained from 60 previously untreated, premenopausal patients with no metastases and with noninflaminatory disease by fine needle sampling without aspiration. We could evaluate DNA ploidy in all patients and SPF in 50 or 83% of them. Tumor responsiveness was significantly related to SPF. The 12 patients who had SPF of 10% or more showed demonstrable regression; six had complete responses. None of the other parameters tested, i.e., DNA ploidy, histopathologic grade, or hormone receptor content, correlated with response. We believe this information may prove valuable for clinicians as they make their decisions regarding patient therapy. [J Nail Cancer Inst 81:1383–1387, 1989] [ABSTRACT FROM PUBLISHER]

An immunoenzymetric assay (IEMA) for the human epidermal growth factor receptor (EGFR) solubilized with nonionic detergent has been developed using two commercially available monoclonal antibodies (MoAb) and tested on breast tumor samples. The first MoAb (R1), immunoadsorbed on a solid phase, is used to immobilize solubilized EGFR. A second MoAb (528) binds to the immobilized EGFR and is revealed with o-phenylenediamine by a peroxidase-linked goat antimouse IgG2a. The detection limit is 2.5 fmol/ml, corresponding to 1-2.5 fmol/mg membrane protein which allows a determination of EGFR from as low as 100-200 μg of membrane proteins. The IEMA was linear for serial sample dilutions in a large range of EGFR concentrations. The recovery of increasing quantities of EGFR added to clinical samples ranged from 82 to 107 %. We found a high reproducibility (r = 0.97) between two successive assays of 36 breast tumor samples. The EGFR content measured by this method in 50 breast tumor samples correlated (r = 0.95) with the values obtained by a radioligand assay on crude membrane preparations. This sensitive, accurate, reproducible, time and tissue quantity efficient IEMA appears suitable for biological and clinical studies of the role of EGFR in malignant pathology. Copyright © 1989 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]