Qualification of a multiplexed tissue imaging assay and detection of novel patterns of HER2 heterogeneity in breast cancer.
Qualification of a multiplexed tissue imaging assay and detection of novel patterns of HER2 heterogeneity in breast cancer.
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DOI：
10.1038/s41523-023-00605-3
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发表时间：
2024-01-02
影响因子：
5.9
通讯作者：
Santagata, Sandro
中科院分区：
文献类型：
--
作者：
Guerriero, Jennifer L.;Lin, Jia-Ren;Pastorello, Ricardo G.;Du, Ziming;Chen, Yu-An;Townsend, Madeline G.;Shimada, Kenichi;Hughes, Melissa E.;Ren, Siyang;Tayob, Nabihah;Zheng, Kelly;Mei, Shaolin;Patterson, Alyssa;Taneja, Krishan L.;Metzger, Otto;Tolaney, Sara M.;Lin, Nancy U.;Dillon, Deborah A.;Schnitt, Stuart J.;Sorger, Peter K.;Mittendorf, Elizabeth A.;Santagata, Sandro
新出现的数据表明，HER2瘤内异质性(ITH)与治疗耐药性有关，这突显了评估HER2 ITH的新策略的必要性。一种很有前途的方法是利用多路组织分析技术，如循环免疫荧光(CyCIF)，它能够在单细胞分辨率下可视化和定量来自单个组织切片的10-60个抗原。在这项研究中，我们鉴定了乳腺癌特异性抗体组合，包括HER2、ER和PR，用于多路组织成像。然后，我们使用像素、细胞和组织水平的分析，利用866个组织核心(代表294名患者)，将这些抗体的性能与已建立的临床标准进行比较。为了确保可靠性，用同一样本的HER2免疫组织化学(IHC)和荧光原位杂交(FISH)数据对CyCIF抗体进行了鉴定。我们的发现证明了针对CyCIF的乳腺癌抗体小组的成功资格，显示出与已建立的临床抗体高度一致。随后，我们利用合格的抗体，以及CD45、CD68、PD-L1、P53、Ki67、pRb和AR的抗体，对189名患者的567例HER2+浸润性乳腺癌样本进行了表征。通过单细胞分析，我们在HER2+乳腺癌中发现了四个不同的细胞群，表现出HER2的异质性表达。此外，这些簇在ER、PR、P53、AR和PD-L1的表达上表现出差异。为了量化异质性的程度，我们根据这些集群之间的多样性计算了异质性分数。我们的分析揭示了与乳腺癌生物学相关的表达模式，与HER2 ITH相关，并与临床结果潜在相关。
Emerging data suggests that HER2 intratumoral heterogeneity (ITH) is associated with therapy resistance, highlighting the need for new strategies to assess HER2 ITH. A promising approach is leveraging multiplexed tissue analysis techniques such as cyclic immunofluorescence (CyCIF), which enable visualization and quantification of 10–60 antigens at single-cell resolution from individual tissue sections. In this study, we qualified a breast cancer-specific antibody panel, including HER2, ER, and PR, for multiplexed tissue imaging. We then compared the performance of these antibodies against established clinical standards using pixel-, cell- and tissue-level analyses, utilizing 866 tissue cores (representing 294 patients). To ensure reliability, the CyCIF antibodies were qualified against HER2 immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) data from the same samples. Our findings demonstrate the successful qualification of a breast cancer antibody panel for CyCIF, showing high concordance with established clinical antibodies. Subsequently, we employed the qualified antibodies, along with antibodies for CD45, CD68, PD-L1, p53, Ki67, pRB, and AR, to characterize 567 HER2+ invasive breast cancer samples from 189 patients. Through single-cell analysis, we identified four distinct cell clusters within HER2+ breast cancer exhibiting heterogeneous HER2 expression. Furthermore, these clusters displayed variations in ER, PR, p53, AR, and PD-L1 expression. To quantify the extent of heterogeneity, we calculated heterogeneity scores based on the diversity among these clusters. Our analysis revealed expression patterns that are relevant to breast cancer biology, with correlations to HER2 ITH and potential relevance to clinical outcomes.
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DOI：
10.1158/1078-0432.ccr-20-3089
发表时间：
2021-02-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Keenan TE;Li T;Vallius T;Guerriero JL;Tayob N;Kochupurakkal B;Davis J;Pastorello R;Tahara RK;Anderson L;Conway J;He MX;Shannon E;Godin RE;Sorger PK;D'Andrea A;Overmoyer B;Winer EP;Mittendorf EA;Van Allen EM;Shapiro GI;Tolaney SM
通讯作者：
Tolaney SM
影响因子：
3.5
作者：
Lee, Hee Jin;Kim, Joo Young;Gong, Gyungyub
通讯作者：
Gong, Gyungyub
影响因子：
--
作者：
Lee, Hee Jin;Song, In Hye;Gong, Gyungyub
通讯作者：
Gong, Gyungyub
影响因子：
3.4
作者：
Baros, Ilija Vladimir;Tanaskovic, Natsa;Tot, Tibor
通讯作者：
Tot, Tibor
影响因子：
82.9
作者：
Binnewies M;Roberts EW;Kersten K;Chan V;Fearon DF;Merad M;Coussens LM;Gabrilovich DI;Ostrand-Rosenberg S;Hedrick CC;Vonderheide RH;Pittet MJ;Jain RK;Zou W;Howcroft TK;Woodhouse EC;Weinberg RA;Krummel MF
通讯作者：
Krummel MF