Søiland Håvard, Skaland Ivar, van Diermen Bianca, Janssen Emiel A M, Körner Hartwig, Varhaug Jan Erik, Søreide Jon Arne, Baak Jan P A
Department of Surgery, Stavanger University Hospital, Stavanger, The Netherlands.
Appl Immunohistochem Mol Morphol. 2008 Jul;16(4):362-70. doi: 10.1097/PAI.0b013e31815b9c92.
Androgen receptor (AR) expression is prognostic for breast cancer. Techniques to determine AR levels include the dextran-coated charcoal method (charc-AR), which measures AR levels in both normal and cancer cells; immunohistochemical analysis (1HC-AR) of whole sections (WS), which targets cancer cells but relies on subjective assay interpretation; and IHC of tissue microarray (TMA) samples, an approach that can be inaccurate when AR heterogeneity is present. This study compared charc-AR (n=151) with quantitative IHC analysis (n=138) of WS and TMA samples (1.7 mm cylinder samples; 2.3 mm). Charc-AR results correlated poorly with IHC-WS and IHC-TMA results due to the presence of AR-positive noncancer cells. IHC-WS revealed intertumor and intratumor AR heterogeneity. Consequently, the IHC-WS and IHC-TMA results were similar for tumors in which the percentage of AR-positive WS samples was >80% (31% of tumors), but differed in other tumors due to TMA false negatives (33%). Computer simulation was used to determine the optimal number and size of TMA samples for reliable results, and showed that five to eight 1.7 mm samples, or up to sixty-four 0.6 mm samples, were needed for reliable AR determination for most tumors. Thus, AR determination by charc-AR is inaccurate due to evaluation of both normal and cancer cells. IHC is more sensitive and specific than charc-AR in WS samples, but not when applied to single or a few TMA samples.
雄激素受体（AR）表达对乳腺癌具有预后价值。测定AR水平的技术包括葡聚糖包被活性炭法（charc-AR），该方法可测量正常细胞和癌细胞中的AR水平；全切片免疫组织化学分析（1HC-AR），其针对癌细胞，但依赖主观的检测解读；以及组织微阵列（TMA）样本的免疫组织化学分析，当存在AR异质性时，这种方法可能不准确。本研究将charc-AR（n = 151）与WS和TMA样本（1.7毫米圆柱样本；2.3毫米）的定量免疫组织化学分析（n = 138）进行了比较。由于存在AR阳性的非癌细胞，charc-AR结果与免疫组织化学-WS和免疫组织化学-TMA结果的相关性较差。免疫组织化学-WS显示肿瘤间和肿瘤内存在AR异质性。因此，对于AR阳性WS样本百分比>80%的肿瘤（占肿瘤的31%），免疫组织化学-WS和免疫组织化学-TMA结果相似，但在其他肿瘤中，由于TMA假阴性（33%），两者结果不同。使用计算机模拟来确定获得可靠结果所需的TMA样本的最佳数量和大小，结果表明，对于大多数肿瘤，需要五到八个1.7毫米样本或多达64个0.6毫米样本才能可靠地测定AR。因此，由于对正常细胞和癌细胞都进行了评估，通过charc-AR测定AR不准确。在WS样本中，免疫组织化学比charc-AR更敏感和特异，但应用于单个或少数TMA样本时并非如此。
