CD8/CD45RO T-cell infiltration in endoscopic biopsies of colorectal cancer predicts nodal metastasis and survival.
CD8/CD45RO T-cell infiltration in endoscopic biopsies of colorectal cancer predicts nodal metastasis and survival.
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DOI：
10.1186/1479-5876-12-81
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发表时间：
2014-03-29
影响因子：
7.4
通讯作者：
Inderbitzin D
中科院分区：
文献类型：
--
作者：
Koelzer VH;Lugli A;Dawson H;Hädrich M;Berger MD;Borner M;Mallaev M;Galván JA;Amsler J;Schnüriger B;Zlobec I;Inderbitzin D
目前缺乏基于结直肠癌（CRC）活检标本的可靠预后标志物。我们推测，对结直肠癌活检组织中T细胞浸润的评估可以预测患者的生存率和手术前的TNM分期。本研究纳入了2002-2011年接受治疗的130例CRC患者的术前活检和匹配切除标本。活检材料和原发性肿瘤的全组织切片进行免疫染色的泛细胞角蛋白和CD 8或CD 45 RO。分析间质和上皮内T细胞浸润以预测患者存活以及原发性肿瘤的临床和病理TNM分期。术前活检中的CD 8 T细胞浸润与良好的总生存率显著相关（CD 8i p = 0.0026; CD 8 s p = 0.0053）与原发性CRC患者的TNM分期和术后治疗无关（HR [CD8i] = 0.55（95% CI：0.36-0.82），p = 0.0038; HR [CD8s] = 0.72（95% CI：0.57-0.9），p = 0.0049）。活检组织中高数量的CD 8i预测较早的PT分期（p < 0.0001）以及原发肿瘤中没有淋巴结转移（p = 0.0015）、肿瘤沉积（p = 0.0117）、淋巴（p = 0.008）和静脉浸润（p = 0.0433）。CD 45 ROs细胞的浸润与更长的生存期独立相关（HR = 0.76（95%CI：0.61-0.96），p = 0.0231），并预测不存在静脉侵袭（p = 0.0025）。CD 8计数在活检和原发肿瘤之间呈正相关（r = 0.42; p < 0.0001），并且在观察者之间是可重复的（ICC [CD 8i] = 0.95，ICC [CD 8 s] = 0.75）。对于CD 45 RO，再现性差至中等（ICC [CD 45 i] = 0.16，ICC [CD 45 s] = 0.49），与原发性肿瘤中免疫浸润的相关性一般且不显著（r[CD 45 s] = 0.16; p = 0.2864）。对于这两种标志物，未观察到与放射学T分期、N分期或M分期的显著关系，表明活检材料中T细胞的评估可为术前临床分期增加额外信息。CRC术前活检标本中的T细胞浸润是一个独立的有利预后因素，与切除标本中无淋巴结转移密切相关。与CD 45 RO相比，CD 8 i的定量具有高度可重复性，并允许对临床病理学特征进行上级预测。建议对活检组织中的CD 8i浸润进行评估以进行前瞻性研究。
Reliable prognostic markers based on biopsy specimens of colorectal cancer (CRC) are currently missing. We hypothesize that assessment of T-cell infiltration in biopsies of CRC may predict patient survival and TNM-stage before surgery. Pre-operative biopsies and matched resection specimens from 130 CRC patients treated from 2002-2011 were included in this study. Whole tissue sections of biopsy material and primary tumors were immunostained for pancytokeratin and CD8 or CD45RO. Stromal (s) and intraepithelial (i) T-cell infiltrates were analyzed for prediction of patient survival as well as clinical and pathological TNM-stage of the primary tumor. CD8 T-cell infiltration in the preoperative biopsy was significantly associated with favorable overall survival (CD8i p = 0.0026; CD8s p = 0.0053) in patients with primary CRC independently of TNM-stage and postoperative therapy (HR [CD8i] = 0.55 (95% CI: 0.36-0.82), p = 0.0038; HR [CD8s] = 0.72 (95% CI: 0.57-0.9), p = 0.0049). High numbers of CD8i in the biopsy predicted earlier pT-stage (p < 0.0001) as well as absence of nodal metastasis (p = 0.0015), tumor deposits (p = 0.0117), lymphatic (p = 0.008) and venous invasion (p = 0.0433) in the primary tumor. Infiltration by CD45ROs cells was independently associated with longer survival (HR = 0.76 (95% CI: 0.61-0.96), p = 0.0231) and predicted absence of venous invasion (p = 0.0025). CD8 counts were positively correlated between biopsies and the primary tumor (r = 0.42; p < 0.0001) and were reproducible between observers (ICC [CD8i] = 0.95, ICC [CD8s] = 0.75). For CD45RO, reproducibility was poor to moderate (ICC [CD45i] = 0.16, ICC [CD45s] = 0.49) and correlation with immune infiltration in the primary tumor was fair and non-significant (r[CD45s] = 0.16; p = 0.2864). For both markers, no significant relationship was observed with radiographic T-stage, N-stage or M-stage, indicating that assessment of T-cells in biopsy material can add additional information to clinical staging in the pre-operative setting. T-cell infiltration in pre-operative biopsy specimens of CRC is an independent favorable prognostic factor and strongly correlates with absence of nodal metastasis in the resection specimen. Quantification of CD8i is highly reproducible and allows superior prediction of clinicopathological features as compared to CD45RO. The assessment of CD8i infiltration in biopsies is recommended for prospective investigation.
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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：
168.9
作者：
Sebag-Montefiore, David;Stephens, Richard J.;Steele, Robert;Monson, John;Grieve, Robert;Khanna, Subhash;Quirke, Phil;Couture, Jean;de Metz, Catherine;Myint, Arthur Sun;Bessell, Eric;Griffiths, Gareth;Thompson, Lindsay C.;Parmar, Mahesh
通讯作者：
Parmar, Mahesh
CD8+淋巴细胞/肿瘤出芽指数：代表结直肠癌中肿瘤宿主相互作用的“促/抗肿瘤”方法的独立预后因素。
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
3.9
作者：
HASE, K;SHATNEY, C;VIERRA, M
通讯作者：
VIERRA, M
影响因子：
168.9
作者：
Gray, Richard;Barnwell, Jennifer;Kerr, David J.
通讯作者：
Kerr, David J.