Association of tumor-infiltrating T-cell density with molecular subtype, racial ancestry and clinical outcomes in prostate cancer.
Association of tumor-infiltrating T-cell density with molecular subtype, racial ancestry and clinical outcomes in prostate cancer.
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DOI：
10.1038/s41379-018-0083-x
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发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Lotan TL
中科院分区：
文献类型：
--
作者：
Kaur HB;Guedes LB;Lu J;Maldonado L;Reitz L;Barber JR;De Marzo AM;Tosoian JJ;Tomlins SA;Schaeffer EM;Joshu CE;Sfanos KS;Lotan TL
炎症微环境在肿瘤的发病机制和进展中起着重要作用，并可能与体细胞基因组改变有关。我们研究了肿瘤浸润性T细胞密度与临床病理变量、肿瘤分子亚型和肿瘤学结局的相关性，这些相关性发生在欧洲裔美国人或非洲裔美国人血统的患者中，这些患者接受了外科治疗。我们评估了312例原发性前列腺肿瘤，其中包括非洲裔美国人和高级别疾病患者。对组织微阵列进行CD 3、CD 8和FOXP 3免疫染色，并使用遗传学验证的方案对ERG和PTEN进行免疫染色。进行图像分析以定量组织微阵列肿瘤斑点中的T细胞密度。组织微阵列点和标准组织切片的含肿瘤区域中T细胞密度的自动定量相关（r=0.73，p<0.00001），并且组织微阵列点上的视觉和自动T细胞密度计数之间具有良好的一致性（r=0.93，p<0.00001）。CD 3+、CD 8+和FOXP 3 + T细胞密度之间存在显著相关性（p<0.00001），但这些与大多数临床或病理变量无关。在匹配的欧洲裔美国人和非洲裔美国人血统患者的联合队列中，T细胞密度增加与ERG阳性（中位数309 vs 188 CD 3 + T细胞/mm 2; p=0.0004）以及PTEN丢失（中位数317 vs 192 CD 3 + T细胞/mm 2; p=0.001）显著相关。当单独分析时，两个祖先的患者中存在相同的关联或相似的趋势。当来自匹配种族集的非裔美国人患者与单独的高级别非裔美国人病例集相结合时，在多变量分析中，FOXP 3 + T细胞密度增加与转移风险增加之间存在弱相关性。虽然高T细胞密度与前列腺癌的特定分子亚类相关，但我们没有发现T细胞密度与种族血统相关。
The inflammatory microenvironment plays an important role in the pathogenesis and progression of tumors and may be associated with somatic genomic alterations. We examined the association of tumor infiltrating T-cell density with clinical-pathologic variables, tumor molecular subtype and oncologic outcomes in surgically-treated primary prostate cancer occurring in patients of European-American or African-American ancestry. We evaluated 312 primary prostate tumors, enriched for patients with African-American ancestry and high grade disease. Tissue microarrays were immunostained for CD3, CD8 and FOXP3 and were previously immunostained for ERG and PTEN using genetically validated protocols. Image analysis for quantification of T-cell density in tissue microarray tumor spots was performed. Automated quantification of T-cell densities in tumor-containing regions of tissue microarray spots and standard histologic sections were correlated (r=0.73, p<0.00001) and there was good agreement between visual and automated T-cell density counts on tissue microarray spots (r=0.93, p<0.00001). There was a significant correlation between CD3+, CD8+ and FOXP3+ T-cell densities (p<0.00001), but these were not associated with most clinical or pathologic variables. Increased T-cell density was significantly associated with ERG positivity (median 309 vs 188 CD3+ T-cells/mm2; p=0.0004) and also with PTEN loss (median 317 vs 192 CD3+ T-cells/mm2; p=0.001) in the combined cohort of matched European-American and African-American ancestry patients. The same association or a similar trend was present in patients of both ancestries when analyzed separately. When the African-American patients from the matched race set were combined with a separate high grade set of African-American cases, there was a weak association of increased FOXP3+ T-cell densities with increased risk of metastasis in multivariable analysis. Though high T-cell density is associated with specific molecular subclasses of prostate cancer, we did not find an association of T-cell density with racial ancestry.
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影响因子：
30.8
作者：
Carver, Brett S.;Tran, Jennifer;Gopalan, Anuradha;Chen, Zhenbang;Shaikh, Safa;Carracedo, Arkaitz;Alimonti, Andrea;Nardella, Caterina;Varmeh, Shohreh;Scardino, Peter T.;Cordon-Cardo, Carlos;Gerald, William;Pandolfi, Pier Paolo
通讯作者：
Pandolfi, Pier Paolo
影响因子：
2.8
作者：
Flammiger, Anna;Bayer, Florian;Trepel, Martin
通讯作者：
Trepel, Martin
影响因子：
5.8
作者：
Lee, Valerie;Murphy, Adrian;Diaz, Luis A., Jr.
通讯作者：
Diaz, Luis A., Jr.
影响因子：
28.2
作者：
Huang FW;Mosquera JM;Garofalo A;Oh C;Baco M;Amin-Mansour A;Rabasha B;Bahl S;Mullane SA;Robinson BD;Aldubayan S;Khani F;Karir B;Kim E;Chimene-Weiss J;Hofree M;Romanel A;Osborne JR;Kim JW;Azabdaftari G;Woloszynska-Read A;Sfanos K;De Marzo AM;Demichelis F;Gabriel S;Van Allen EM;Mesirov J;Tamayo P;Rubin MA;Powell IJ;Garraway LA
通讯作者：
Garraway LA
影响因子：
30.8
作者：
King, Jennifer C.;Xu, Jin;Wongvipat, John;Hieronymus, Haley;Carver, Brett S.;Leung, David H.;Taylor, Barry S.;Sander, Chris;Cardiff, Robert D.;Couto, Suzana S.;Gerald, William L.;Sawyers, Charles L.
通讯作者：
Sawyers, Charles L.