Institute of Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstaedter Landstr. 1, 85764 Neuherberg, Germany.
BMC Cancer. 2010 Nov 5;10:608. doi: 10.1186/1471-2407-10-608.
The validation of novel prognostic indicators is of greatest interest for the management of esophageal adenocarcinoma (Barrett's cancer), particularly for non-metastasized (stage I-IIA) disease. The prognostic role of tumor infiltrating T-lymphocytes (TILs) in Barrett's cancer has not been reported so far. Here we evaluated the impact of TILs on survival, recurrence, and metastasis in Barrett's cancer, particularly in stage I-IIA patients.
The levels of the adaptive immune markers CD3, CD8, and CD45RO were analyzed by immunohistochemistry and image analysis in tissue microarrays consisting of tumor tissues of 118 patients with primary resected Barrett's cancer. The findings were correlated with clinicopathological parameters including patient outcome.
In multivariate analysis, a low density of intratumoral CD45RO+ immune cells was an independent unfavorable factor for disease-free survival in stages I-IIA patients (P = 0.004, RR = 4.7, 95% CI = 1.6-13.5) as well in the entire cohort (P = 0.048, RR = 2.0, 95% CI = 1.0-4.0). High CD3+ and CD45RO+ levels were associated with prolonged disease-free survival and overall survival as well with low recurrence rates of disease (P = 0.005 and P = 0.018, respectively). In addition, low CD3+ levels were correlated with a higher frequency of lymph node metastasis (P = 0.025).
This study demonstrates that the density of CD45RO+ TILs is an independent prognostic factor in non-metastasized (stage I-IIA) Barrett's cancer patients and indicates an important role for the adaptive immunologic microenvironment. The inclusion of CD45RO+ density may help to improve the management of stage I-IIA Barrett's cancer.
新型预后标志物的验证对于食管腺癌(巴雷特癌)的管理最为重要,特别是对于非转移性(I 期-IIA 期)疾病。到目前为止,肿瘤浸润 T 淋巴细胞(TILs)在巴雷特癌中的预后作用尚未报道。在这里,我们评估了 TILs 在巴雷特癌中的生存、复发和转移中的作用,特别是在 I 期-IIA 期患者中。
通过免疫组织化学和组织微阵列中的图像分析,分析了 118 例原发性切除巴雷特癌患者肿瘤组织中适应性免疫标志物 CD3、CD8 和 CD45RO 的水平。将这些发现与包括患者结局在内的临床病理参数相关联。
在多变量分析中,肿瘤内 CD45RO+免疫细胞密度低是 I 期-IIA 期患者无病生存的独立不良因素(P = 0.004,RR = 4.7,95%CI = 1.6-13.5),以及整个队列中(P = 0.048,RR = 2.0,95%CI = 1.0-4.0)。高 CD3+和 CD45RO+水平与无病生存和总生存延长以及疾病复发率降低相关(P = 0.005 和 P = 0.018)。此外,低 CD3+水平与更高的淋巴结转移频率相关(P = 0.025)。
这项研究表明,CD45RO+TILs 的密度是非转移性(I 期-IIA 期)巴雷特癌患者的独立预后因素,并表明适应性免疫微环境的重要作用。CD45RO+密度的纳入可能有助于改善 I 期-IIA 期巴雷特癌的管理。