ESTROGEN-RECEPTOR IMMUNOSTAINING PATTERNS IMAGED IN BREAST-CANCER FINE-NEEDLE ASPIRATES

Fine needle aspirates (FNA) after estrogen receptor (peroxidase-antiperoxidase) immunostaining were imaged using a SAMBA system. Integrated optical density (IOD) and mean optical density (MOD) was measured in individual nuclei. Receptogram A Analytic software on a remote VAX computer teas used to generate log-log scatter, contour and three-dimensional perspective plots of bivariate MOD vs. IOD relationships and for count-dependent Gaussian smoothing of the univariate log histograms. The findings revealed four types of Staining patterns among otherwise estrogen receptor immunostaining-positive patients: (I) a discrete, homogeneous subpopulation with unimodal MOD and IOD distributions; (II) coexistent subpopulations of ER+ and EX- cells, revealed by bivariate MOD and IOD distributions; (III) multiple, discrete subpopulations of ER+ cells, revealed in perspective plots of MOD vs. IOD vs. scatter density; and (TV) highly skewed distributions forming a continuum over a broad MOD and IOD range with or without an EX-negative subpopulation. FNA EX-ICA-positive specimens were indistinguishable based upon average nuclear MOD (AV-MOD) or AV-MOD X (% ER-positive cells). Previous evaluation of such patterns in tissue sections revealed failure of tamoxifen response in types II and IV. Staining mosaicism (IV) may correspond to a failure of receptor modulation within defined limits when ER is rendered nonfunctional due to various structural modifications of receptor domains-events that would not affect immunostaining. Failure in type II is ascribed to ascendancy of estrogen-independent ER-negative subpopulations.