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 R Analytic software on a remote VAX computer was 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 ER- 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 (IV) highly skewed distributions forming a continuum over a broad MOD and IOD range with or without an ER-negative subpopulation. FNA ER-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.
Sklarew
R J
RJ
Department of Medicine, New York Medical College, Elmsford 10523.
Wali
R
R
Auger
M
M
Kidd
L D
LD
Katz
R L
RL
D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000295:instrumentation / Q000379:methods*; D007150:Immunohistochemistry / Q000379:methods*; D011960:Receptors, Estrogen / Q000302:isolation & purification*
D011960:Receptors, Estrogen