Lavotshkin Simon, Jalas John R, Torisu-Itakura Hitoe, Ozao-Choy Junko, Lee Ji Hey, Sim Myung Shin, Stojadinovic Alexander, Wainberg Zev, Bifulco Carlo B, Fox Bernard A, Bilchik Anton J
Department of Surgical Oncology, The John Wayne Cancer Institute at Providence Saint John's Health Center, 2200 Santa Monica Blvd., Santa Monica, CA, 90404, USA.
J Gastrointest Surg. 2015 Jun;19(6):999-1006. doi: 10.1007/s11605-015-2759-6. Epub 2015 Mar 26.
Although AJCC/TNM staging remains the gold standard for prognostic assessment of colon cancer, stage-specific outcomes vary. We therefore prospectively evaluated the prognostic role of immunoprofiling.
Our cohort included 35 patients from an ongoing prospective trial of ultrastaging for colon cancer. Specimens were analyzed for T cell markers (CD3, CD4, CD8, and FoxP3). The number of tumor-infiltrating lymphocytes was analyzed at the tumor's margin and center and correlated with AJCC/TNM stage, clinicopathologic variables, and disease-free survival.
There was a significant inverse association between number of CD3(+) cells in the tumor center and tumor stage (P = 0.05). The tumor center/margin ratio of CD3(+) cells also showed an inverse but non-significant relationship with nodal involvement (P = 0.07). Body mass index was inversely associated with numbers of CD3(+)(P = 0.04) and CD8(+)(P = 0.02) cells. Longer disease-free survival was correlated with higher CD8+ counts (P = 0.07), lower CD4(+)/CD8(+) ratios (P = 0.008), and higher CD8(+)/FoxP3(+) ratios (P = 0.02).
This is the first prospective validation of immunoprofiling in patients whose colon cancer is staged with strict surgical and pathology quality measures. The apparent correlation between immunophenotypic response and clinical outcome warrants evaluation in a larger prospective trial.
尽管美国癌症联合委员会（AJCC）/国际抗癌联盟（TNM）分期仍是结肠癌预后评估的金标准，但特定分期的预后结果存在差异。因此，我们前瞻性地评估了免疫表型分析的预后作用。
我们的队列包括35名正在进行的结肠癌超分期前瞻性试验的患者。对标本进行T细胞标志物（CD3、CD4、CD8和FoxP3）分析。在肿瘤边缘和中心分析肿瘤浸润淋巴细胞的数量，并将其与AJCC/TNM分期、临床病理变量和无病生存期相关联。
肿瘤中心CD3(+)细胞数量与肿瘤分期之间存在显著负相关（P = 0.05）。CD3(+)细胞的肿瘤中心/边缘比值与淋巴结受累也呈负相关，但无统计学意义（P = 0.07）。体重指数与CD3(+)（P = 0.04）和CD8(+)（P = 0.02）细胞数量呈负相关。更长的无病生存期与更高的CD8+计数（P = 0.07）、更低的CD4(+)/CD8(+)比值（P = 0.008）和更高的CD8(+)/FoxP3(+)比值（P = 0.02）相关。
这是首次对采用严格手术和病理质量标准分期的结肠癌患者进行免疫表型分析的前瞻性验证。免疫表型反应与临床结果之间的明显相关性值得在更大规模的前瞻性试验中进行评估。
