Beatty Barbara G, Bryant Ronald, Wang Weichen, Ashikaga Takamaru, Gibson Pamela C, Leiman Gladwyn, Weaver Donald L
Department of Pathology, University of Vermont College of Medicine, Burlington 05405-0068, USA.
Am J Clin Pathol. 2004 Aug;122(2):246-55. doi: 10.1309/N82C-TQ1J-0XEV-EFQB.
We evaluated HER-2 receptor status by immunocytochemical and immunohistochemical analyses and fluorescence in situ hybridization (FISH) in 51 fine-needle aspiration (FNA) specimens together with the corresponding formalin-fixed, paraffin-embedded (FFPE) tissue samples obtained from surgically resected breast cancers. Three fixation methods were compared: ethanol, formalin, and CytoLyt-ThinPrep (Cytyc, Boxborough, MA). HER-2 was overexpressed and amplified in 8 (16%) of 51 FFPE specimens. Of the 8 cases, gene amplification was observed in 8 FNA specimens (100%) and overexpression in 2 (25%) ethanol-, 4 (50%) CytoLyt-, and 5 (63%) formalin-fixed FNA specimens. Strong pairwise kappa association between FISH results performed on FNA specimens and FFPE tissue samples (ethanol fixation, kappa = 0.848; ThinPrep, kappa = 0.918) and moderate (ThinPrep, kappa = 0.692; formalin fixation, kappa = 0.667) to poor (ethanol, kappa = 0.300) pairwise kappa agreement between tissue immunohistochemical and FNA immunocytochemical results was demonstrated. We conclude that HER-2 protein expression on cytologic preparations was insufficiently reliable for clinical use, whereas HER-2 gene amplification determined by FISH demonstrated strong and consistent correlation with HER-2 status of FFPE tissue samples.
我们通过免疫细胞化学、免疫组织化学分析以及荧光原位杂交（FISH）对51份细针穿刺（FNA）标本以及相应的取自手术切除乳腺癌的福尔马林固定、石蜡包埋（FFPE）组织样本进行了HER-2受体状态评估。比较了三种固定方法：乙醇、福尔马林和CytoLyt-ThinPrep（Cytyc公司，马萨诸塞州博克斯伯勒）。在51份FFPE标本中，有8份（16%）HER-2呈过表达和扩增。在这8例中，8份FNA标本（100%）观察到基因扩增，2份（25%）乙醇固定、4份（50%）CytoLyt固定和5份（63%）福尔马林固定的FNA标本中观察到过表达。对FNA标本和FFPE组织样本进行的FISH结果之间存在强的成对kappa关联（乙醇固定，kappa = 0.848；ThinPrep，kappa = 0.918），并且组织免疫组织化学和FNA免疫细胞化学结果之间的成对kappa一致性从中度（ThinPrep，kappa = 0.692；福尔马林固定，kappa = 0.667）到差（乙醇，kappa = 0.300）。我们得出结论，细胞学标本上的HER-2蛋白表达在临床应用中可靠性不足，而通过FISH确定的HER-2基因扩增与FFPE组织样本的HER-2状态显示出强且一致的相关性。
