""""""""Receptogram Analysis"""""""" has been developed to evaluate the prognostic significance of estrogen receptor patterns in breast cancer cryostat sections based upon quantitative imaging of the immunocytochemical assay (ERICA). It has demonstrated significantly higher sensitivity and specificity than cytosol assays (DCC) in predicting response to Tamoxifen and endocrine therapy in stage III and IV disease. Identification of responders and non-responders is based upon typing nuclear ER content and concentration distributions and their bivariate contour patterns. The biologic basis for criticality of the typing patterns remains to be determined. The analysis has been extended to progesterone receptors (PgRICA). ERICA and PgRICA sections are evaluable for imaging in 100 post menopausal, stage II patients for retrospective correlation of Receptograms with histopathology, DCC, and DNA ploidy/S-phase fraction (SPF), determined by flow cytometry. Fine needle aspirates will be evaluated prospectively in Stage III/IV geriatric breast cancer patients (50/yr) receiving Tamoxifen for at least 8 weeks. Smear or cytocentrifuge preparations will be prepared for ERICA and PgRICA imaging and after 3HTdR pulse labeling in vitro. Cells mapped during receptor analysis will be relocated subsequently for imaging in Feulgen-stained autoradiographs. DNA ploidy status (DNA indices, DI), thymidine labeling indices (LI), and grain counts over S-phase nuclei will be determined simultaneously by densitometric imaging, and correlated with ER and PgR in individual nuclei. Identification of labeled S cells aids resolution of the cell cycle phase distribution of ploidy subpopulations. The hypothesis is advances that receptograms reflect not only steroid receptor status but also the ploidy and proliferative characteristics (DI, LI and SPF) of breast cancers. As prognostic indicators these correlate independently with recurrence, disease-free interval and survival. Their congruence with specific Receptogram patterns will provide the rationale for Receptogram response prediction and the development of receptogram and/or multiple discriminants for these end points. Aspiration biopsy is a useful and cost effective method for monitoring tumor lesions in outpatients. The proposed microscopic methods for multiparameter analysis are particularly well suited for prognostic evaluation of lesions which are too small to provide adequate cells for DCC or flow cytometry.
| Sklarew, R J; Wali, R; Auger, M et al. (1994) Estrogen receptor immunostaining patterns imaged in breast cancer fine needle aspirates. Anal Quant Cytol Histol 16:293-305 |
