Metadata and data supporting the published article: Association between Low Estrogen Receptor Positive Breast Cancer and Staining Performance

Using digital analysis and quantitative tools, the authors compared the dynamic range of nuclear estrogen receptor (ER) expression in normal background ductal profiles in patients with low (1-10%) ER tumors, to the dynamic range of ER expression in normal epithelium from control patient populations (using a normal benign breast tissue (TMA) and sections of clinical control tumour cases), to determine if low ER cases are accompanied by decreased dynamic range.<br><b>Data access</b>: Dataset <b>Prelim TMA v Low ER Data Summary.csv </b>supporting figures 2 and 3 of the published article, is publicly available as part of this figshare data record (<b>https://doi.org/10.6084/m9.figshare.11482665</b>). Dataset low ER and control patient and tumor data.xlsx supporting table 1 of the published article is not publicly available in order to protect patient privacy, but can be made available on reasonable request from the corresponding author Dr. Emily Reisenbichler; Yale School of Medicine; Assistant Professor, Department of Pathology; email: <b>[e-mail]</b>.<br><b>Study approval and patient consent</b>: Tissue and associated clinico-pathological information were used after approval from the Yale Human Investigation Committee (protocol # 9505008219). Given the retrospective nature of the study, a waiver of written consent was granted.<br><b>Study aims and methodology</b>: This study aimed to examine the association between low estrogen receptor positive breast cancer and staining performance. The authors hypothesized that low ER positive cases may sometimes be a result of poor staining performance and that it may be possible to detect this artefact by assessing the average dynamic range of normal ducts adjacent to low ER positive tumors.<br>The pathology database search identified that ER immunohistochemistry (IHC) was performed on 3786 cases of invasive breast carcinomas following the updated 2010 ASCO/CAP guidelines, 40 (1.05%) of which were reported as demonstrating low (1-10%) ER expression. Glass slides of the original ER stained sections were retrieved from the archive for digital scanning.Two different normal controls were used. The first control set utilized a tissue microarray (TMA), YTMA-55, constructed of tissue obtained from the archives of the Pathology Department at Yale University, consisting of 0.6 mm cores of normal breast tissue collected in 1981 and 1982. This set was utilized as a normal level of ER expression in benign breast tissue. The second group of normal control cases included benign background epithelium from sections of invasive breast carcinomas tested for ER by IHC in the Yale clinical laboratory.<br>The number of samples used in the study is as follows:Low ER tumor patient samples = 21Control ER tumor patient samples = 34Normal breast patient samples = 10<br>For details on the immunohistochemistry procedure, quantitation of the immunohistochemistry images and statistical analysis, please read the published article.<br><b>Data supporting the figures and tables in the published article</b>: Dataset <b>Prelim TMA v Low ER Data Summary.csv</b> is in <b>.csv </b>file format and supports figures 2 and 3 of the published article. The table consists of 5 columns:Column “Centroid” consists of computer-generated numbers that were not used.Column “id” lists the “id” with each individual number representing a separate breast/patient. Each row within a single patient case number represents a separate ductal profile evaluated for the specimen (for example, rows 2-4 represent the readings from 3 separate ductal profiles on case/patient sample 1).Column “group” reports the name of the testing cohort that each case belongs to (YTMA was benign normal tissue control subset; Low ER was the clinical study set; Normal ER is the control clinical tumor cases)<br>Column “Nuclear DAB OD mean” shows the mean nuclear optical density reading of the nuclear staining seen within the specific ductal profileColumn “Pos Obj Ct” shows the the number of individual nuclei with detectable staining in that particular ductal profile.<br>Dataset <b>low ER and control patient and tumor data.xlsx </b>is in <b>.xlsx</b> file format and supports table 1 of the published article. The dataset contains patient information (including demographics and clinicopathologic tumour features).<br>研究团队采用数字化分析与定量手段，对比了低（1%~10%）雌激素受体（estrogen receptor, ER）表达肿瘤患者的正常背景导管轮廓中核ER表达的动态范围，与对照组人群正常上皮组织的ER表达动态范围（对照组采用正常良性乳腺组织组织微阵列（Tissue Microarray, TMA）及临床对照肿瘤病例切片），以明确低ER表达病例是否伴随动态范围降低。<br><b>数据获取</b>：支撑该已发表论文图2与图3的数据集<b>Prelim TMA v Low ER Data Summary.csv</b>，可作为本figshare数据记录的组成部分公开获取（<b>https://doi.org/10.6084/m9.figshare.11482665</b>）。支撑该已发表论文表1的数据集<b>low ER and control patient and tumor data.xlsx</b>因需保护患者隐私暂未公开，但若提出合理请求，可向通讯作者Emily Reisenbichler博士申请获取；该博士任职于耶鲁医学院（Yale School of Medicine）病理学系，职称助理教授，电子邮箱：<b>[e-mail]</b>。<br><b>研究伦理批准与患者知情同意</b>：本研究使用的组织及相关临床病理信息已获得耶鲁大学人类研究委员会批准（协议编号：# 9505008219）。鉴于本研究为回顾性研究，已获批豁免书面知情同意程序。<br><b>研究目的与方法学</b>：本研究旨在探究低雌激素受体阳性乳腺癌与染色效果之间的关联。研究团队提出假说：部分低ER阳性病例可能源于染色效果不佳，且可通过评估低ER阳性肿瘤旁正常导管的平均动态范围来检测此类人工假象。<br>通过病理数据库检索发现，按照2010年更新的美国临床肿瘤学会/美国病理学家协会（ASCO/CAP）指南，共完成3786例浸润性乳腺癌的ER免疫组织化学（Immunohistochemistry, IHC）检测，其中40例（占比1.05%）被报告为低（1%~10%）ER表达。研究团队从档案库中调取原始ER染色切片的玻璃玻片进行数字化扫描。<br>本研究采用两类不同的正常对照样本：第一类对照集使用组织微阵列YTMA-55，该阵列构建自耶鲁大学病理学系档案库中的组织，包含1981年与1982年采集的0.6mm直径正常乳腺组织芯，用于代表良性乳腺组织中ER表达的正常水平；第二类正常对照病例则来自耶鲁临床实验室中经IHC检测ER的浸润性乳腺癌切片中的良性背景上皮组织。<br>本研究使用的样本量如下：低ER肿瘤患者样本=21例；对照ER肿瘤患者样本=34例；正常乳腺患者样本=10例。<br>关于免疫组织化学实验流程、免疫组织化学图像定量分析及统计学分析的详细信息，请参阅已发表的研究论文。<br><b>支撑已发表论文图表的数据集说明</b>：数据集<b>Prelim TMA v Low ER Data Summary.csv</b>为逗号分隔值（CSV）格式，用于支撑该已发表论文的图2与图3。该表格包含5列：<br>列“Centroid”：由计算机生成的数值，未在分析中使用。<br>列“id”：列出样本编号，每个单独数字代表独立的乳腺/患者样本。单个患者病例编号对应的多行数据代表该标本中评估的独立导管轮廓（例如，第2~4行代表患者样本1的3个独立导管轮廓的检测结果）。<br>列“group”：标注每个样本所属的试验队列名称（YTMA为良性正常组织对照亚组；Low ER为临床研究队列；Normal ER为临床肿瘤对照病例）。<br>列“Nuclear DAB OD mean”：显示特定导管轮廓内核染色的平均核光密度读数。<br>列“Pos Obj Ct”：显示该特定导管轮廓中可检测到染色的单个细胞核数量。<br>数据集<b>low ER and control patient and tumor data.xlsx</b>为Excel（XLSX）格式，用于支撑该已发表论文的表1。该数据集包含患者信息（包括人口统计学资料与临床病理肿瘤特征）。