Sklarew R J, Wali R, Auger M, Kidd L D, Katz R L
Department of Medicine, New York Medical College, Elmsford 10523.
Anal Quant Cytol Histol. 1994 Aug;16(4):293-305.
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.
对雌激素受体（过氧化物酶-抗过氧化物酶）免疫染色后的细针穿刺抽吸物（FNA）使用SAMBA系统进行成像。在单个细胞核中测量积分光密度（IOD）和平均光密度（MOD）。使用远程VAX计算机上的Receptogram R分析软件生成双变量MOD与IOD关系的对数-对数散点图、等高线图和三维透视图，并对单变量对数直方图进行计数依赖的高斯平滑处理。研究结果显示，在其他方面雌激素受体免疫染色呈阳性的患者中存在四种染色模式：（I）具有单峰MOD和IOD分布的离散、均匀亚群；（II）通过双变量MOD和IOD分布揭示的ER+和ER-细胞共存亚群；（III）在MOD与IOD与散射密度的透视图中显示的多个离散ER+细胞亚群；以及（IV）在较宽的MOD和IOD范围内形成连续体的高度偏态分布，有或没有ER阴性亚群。基于平均细胞核MOD（AV-MOD）或AV-MOD×（ER阳性细胞百分比），FNA ER-ICA阳性标本无法区分。先前在组织切片中对这些模式的评估显示，II型和IV型患者对他莫昔芬无反应。当由于受体结构域的各种结构修饰使ER失去功能时，染色镶嵌（IV型）可能对应于在限定范围内受体调节的失败——这些事件不会影响免疫染色。II型失败归因于雌激素非依赖性ER阴性亚群的优势。
