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Association between low estrogen receptor positive breast cancer and staining performance.
npj Breast Cancer ( IF 6.5 ) Pub Date : 2020-02-05 , DOI: 10.1038/s41523-020-0146-2
Dennis Caruana 1 , Wei Wei 2 , Sandra Martinez-Morilla 1 , David L Rimm 1, 3 , Emily S Reisenbichler 1
Affiliation  

Estrogen receptor (ER) expression in breast carcinomas, determined by immunohistochemistry, indicates statistically significant benefit to endocrine therapy in patients with tumors expressing ER in ≥1% of tumor cells. Rare cases with low ER expression (1-10%) lead to the dilemma of treating these tumors as ER positive or negative. We hypothesize that low ER positive result from poor staining performance and that we may detect this artefact by assessing the average dynamic range of normal ducts adjacent to low ER positive tumors. Using quantitative tools, we compare the dynamic range of normal background ER expression in patients with low (1-10%) ER tumors to dynamic range of ER expression in normal epithelium from control patient populations, to determine if low ER cases are accompanied by decreased dynamic range. Low ER cases were infrequent (1% of invasive breast carcinomas). Twenty-one cases with low ER staining and two control cohorts, including a tissue microarray (TMA) of 10 benign breast sections and a group of 34 control breast carcinomas (reported as ER negative or >10% ER positive) with normal background epithelium, were digitally scanned. QuPath was utilized to quantify ER staining for each cell as the mean optical density of nuclear DAB staining. The dynamic range of ER expression in normal epithelium surrounding low ER tumors was significantly lower (range 2-240, median 16.5) than that of the benign epithelium in the control tumors (range 3-475, median 30.8; p < 0.001) and benign TMA sections (range 38-212, median 114; p < 0.001) suggesting inconsistent stainer performance.

中文翻译:


低雌激素受体阳性乳腺癌与染色性能之间的关联。



通过免疫组织化学测定的乳腺癌中雌激素受体 (ER) 的表达表明,对于肿瘤细胞中表达 ER ≥1% 的肿瘤患者,内分泌治疗具有统计学上显着的益处。 ER 低表达的罕见病例(1-10%)导致将这些肿瘤治疗为 ER 阳性或阴性的困境。我们假设低 ER 阳性是由于染色性能差造成的,并且我们可以通过评估与低 ER 阳性肿瘤相邻的正常导管的平均动态范围来检测这种假象。使用定量工具,我们将低 (1-10%) ER 肿瘤患者的正常背景 ER 表达的动态范围与对照患者群体的正常上皮中 ER 表达的动态范围进行比较,以确定低 ER 病例是否伴有降低动态范围。低 ER 病例并不常见(占浸润性乳腺癌的 1%)。 21 个低 ER 染色病例和两个对照队列,包括 10 个良性乳腺切片的组织微阵列 (TMA) 和一组 34 个具有正常背景上皮的对照乳腺癌(报告为 ER 阴性或 >10% ER 阳性),进行了数字扫描。 QuPath 用于量化每个细胞的 ER 染色,作为核 DAB 染色的平均光密度。低 ER 肿瘤周围正常上皮的 ER 表达动态范围(范围 2-240,中位数 16.5)显着低于对照肿瘤中的良性上皮(范围 3-475,中位数 30.8;p < 0.001)和良性上皮。 TMA 切片(范围 38-212,中位数 114;p < 0.001)表明染色剂性能不一致。
更新日期:2020-02-05
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