Technical Feasibility of Tissue Microarray (TMA) Analysis of Tumor-Associated Immune Response in Prostate Cancer.
Technical Feasibility of Tissue Microarray (TMA) Analysis of Tumor-Associated Immune Response in Prostate Cancer.
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DOI：
10.7150/jca.22846
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发表时间：
2018
影响因子：
3.9
通讯作者：
Stojadinovic A
中科院分区：
文献类型：
--
作者：
Wallace TJ;Qian J;Avital I;Bay C;Man YG;Wellman LL;Moskaluk C;Troyer D;Ramnani D;Stojadinovic A
前言：雄激素受体(AR)调节免疫相关的上皮间充质转化(EMT)和前列腺癌(PCa)转移。原发肿瘤浸润性淋巴细胞(TIL)[CD3+、CD4+和CD8+TIL]是PCa的潜在预后指标，变异可能导致肿瘤生物学和PCa预后的种族差异。目的：评估基于肿瘤微阵列(TMA)的方法在一期切除的PCa中进行多标记TIL分析的技术可行性。方法：40例经病理证实的原发性前列腺癌石蜡包埋组织芯(n=40，1例TMA组织标本丢失)，在TMA上排列成三份。采用免疫组织化学方法检测AR、CD3+、CD4+、CD8+TIL在正常前列腺、肿瘤占优势结节中心和周边及最高Gleason分级中的表达情况，并与临床病理资料进行统计学分析。一位独立的病理学家对临床数据视而不见，对所有样本(阳性细胞的百分比和强度)进行了评分。结果：21例(53.8%)黑人男性和18例(46.2%)白人男性Pca完全切除[pT2a(n=3；7.7%)；pT2b(n=2；5.1%)；pT2c(n=27；69.2%)；pT3a(n=5；12.8%)；术前平均PSA=8.17 ng/ml]。CD3、CD4、CD8和CD8/CD3细胞蛋白在显性结节周围、最高Gleason分级中心和最高Gleason分级周围的表达与正常相比有显著差异(P<；0.05)。TIL在显性结节中心和周边的表达分别与最高Gleason分级的相应中心和周边之间的相关性很强，而且这些相关性的程度因种族而显著不同(P<；0.05)。结论：多标记物(AR、CD3、CD4、CD8)结合IHC分析对原发癌、非转移性前列腺癌的TMA进行分析在技术上是可行的。未来的研究将使用半定量的基于IHC的方法来评估原发肿瘤免疫评分，以评估TIL的频谱、数量和/或定位的差异，并深入了解PCa肿瘤生物学和临床结果的种族差异。
Introduction: The androgen receptor (AR) regulates immune-related epithelial-to-mesenchymal transition (EMT), and prostate cancer (PCa) metastasis. Primary tumor-infiltrating lymphocytes (TILs) [CD3+, CD4+, and CD8+ TILs] are potential prognostic indicators in PCa, and variations may contribute to racial disparities in tumor biology and PCa outcomes. Aim: To assess the technical feasibility of tumor microarray (TMA)-based methods to perform multi-marker TIL profiling in primary resected PCa. Methods: Paraffin-embedded tissue cores of histopathologically-confirmed primary PCa (n = 40; 1 TMA tissue specimen loss) were arrayed in triplicate on TMAs. Expression profiles of AR, CD3+, CD4+, and CD8+ TILs in normal prostate, and the center and periphery of both the tumor-dominant nodule and highest Gleason grade were detected by IHC and associated with clinical and pathological data using standard statistical methodology. An independent pathologist, blinded to the clinical data, scored all samples (percent and intensity of positive cells). Results: TMAs were constructed from 21 (53.8%) Black and 18 (46.2%) White males with completely-resected, primarily pT2 stage PCa [pT2a (n = 3; 7.7%); pT2b (n = 2; 5.1%); pT2c (n = 27; 69.2%); pT3a (n = 5; 12.8%); mean pre-op PSA = 8.17 ng/ml]. The CD3, CD4, CD8, and CD8/CD3 cellular protein expression differed from normal in the periphery of the dominant nodule, the center of the highest Gleason grade, and the periphery of the highest Gleason grade (P < 0.05). Correlations between TIL expression in the center and periphery of the dominant nodule, with corresponding center and periphery of the highest Gleason grade, respectively, were robust, and the magnitude of these correlations differed markedly by race (P < 0.05). Conclusions: Multi-marker (AR, CD3, CD4, CD8) profiling with IHC analysis of TMAs consisting of primary, non-metastatic resected prostate cancer is technically feasible in this pilot study. Future studies will evaluate primary tumor immunoscore using semi-quantitative, IHC-based methodology to assess differences in the spectrum, quantity, and/or localization of TILs, and to gain insights into racial disparities in PCa tumor biology and clinical outcomes.
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影响因子：
7.4
作者：
Galon J;Pagès F;Marincola FM;Angell HK;Thurin M;Lugli A;Zlobec I;Berger A;Bifulco C;Botti G;Tatangelo F;Britten CM;Kreiter S;Chouchane L;Delrio P;Arndt H;Asslaber M;Maio M;Masucci GV;Mihm M;Vidal-Vanaclocha F;Allison JP;Gnjatic S;Hakansson L;Huber C;Singh-Jasuja H;Ottensmeier C;Zwierzina H;Laghi L;Grizzi F;Ohashi PS;Shaw PA;Clarke BA;Wouters BG;Kawakami Y;Hazama S;Okuno K;Wang E;O'Donnell-Tormey J;Lagorce C;Pawelec G;Nishimura MI;Hawkins R;Lapointe R;Lundqvist A;Khleif SN;Ogino S;Gibbs P;Waring P;Sato N;Torigoe T;Itoh K;Patel PS;Shukla SN;Palmqvist R;Nagtegaal ID;Wang Y;D'Arrigo C;Kopetz S;Sinicrope FA;Trinchieri G;Gajewski TF;Ascierto PA;Fox BA
通讯作者：
Fox BA
影响因子：
8.4
作者：
Droeser, Raoul A.;Hirt, Christian;Tornillo, Luigi
通讯作者：
Tornillo, Luigi
影响因子：
6.6
作者：
Gaston, KE;Kim, D;Mohler, JL
通讯作者：
Mohler, JL
影响因子：
158.5
作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
通讯作者：
Young, J.
影响因子：
7.5
作者：
Davidsson, Sabina;Ohlson, Anna-Lena;Rider, Jennifer R.
通讯作者：
Rider, Jennifer R.