Two-marker protein profile predicts poor prognosis in patients with early rectal cancer.
Two-marker protein profile predicts poor prognosis in patients with early rectal cancer.
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DOI：
10.1038/sj.bjc.6604729
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发表时间：
2008-11-18
影响因子：
8.8
通讯作者：
Lugli, A.
中科院分区：
文献类型：
--
作者：
Zlobec, I.;Baker, K.;Terracciano, L.;Peter, S.;Degen, L.;Beglinger, C.;Lugli, A.
本研究的目的是建立一个免疫组化蛋白质谱，以补充术前分期，并确定直肠癌患者的不良后果的高风险。在包括482个直肠癌的组织微阵列上进行APAF-1、EphB 2、MST 1、Ki 67、p53、RHAMM、RKIP和CD 8+肿瘤浸润淋巴细胞（TIL）的免疫组织化学。在数据重新整理和多变量分析后，将最可重复的标志物组合，并根据pT和pN状态分层评估预后。多因素分析中，仅RHAMM阳性（P<0.001; HR=1.94（1.44-2.61））和CD 8 + TIL缺失（P=0.006; HR=0.63（0.45-0.88））是独立的预后因素。RHAMM+/TIL−患者的5年癌症特异性生存率为30%（95% CI：21-40%），而RHAMM−/TIL+患者为76%（95% CI：66-84%）（P<0.001）。T1/T2/RHAMM+/TIL−患者的5年癌症特异性生存率为48%（20-72%），显著低于T3/T4/RHAMM−/TIL+患者（71%，95% CI 56-82%; P=0.039）。按淋巴结状态分层，只有N+/RHAMM+/TIL-患者的预后显著差于N 0/RHAMM+/TIL-患者（P=0.005）。仅在RHAMM+肿瘤中，CD 8 + TILs的缺失预测局部复发（P=0.009）。RHAMM和CD 8 + TIL可能有助于识别面临特别差预后的早期直肠癌患者，这些患者可能从术前治疗中获益。
The aim of this study was to establish an immunohistochemical protein profile to complement preoperative staging and identify rectal cancer patients at high-risk of adverse outcome. Immunohistochemistry was performed on a tissue microarray including 482 rectal cancers for APAF-1, EphB2, MST1, Ki67, p53, RHAMM, RKIP and CD8+ tumour infiltrating lymphocytes (TILs). After resampling of the data and multivariable analysis, the most reproducible markers were combined and prognosis evaluated as stratified by pT and pN status. In multivariable analysis, only positive RHAMM (P<0.001; HR=1.94 (1.44–2.61)) and loss of CD8+ TILs (P=0.006; HR=0.63 (0.45–0.88)) were independent prognostic factors. The 5-year cancer-specific survival rate for RHAMM+/TIL− patients was 30% (95% CI 21–40%) compared to 76% (95% CI: 66–84%) for RHAMM−/TIL+ patients (P<0.001). The 5-year cancer-specific survival of T1/T2/RHAMM+/TIL− patients was 48% (20–72%) and significantly worse compared to T3/T4/RHAMM−/TIL+ patients (71% 95% CI 56–82%); P=0.039). Stratifying by nodal status, only N+/RHAMM+/TIL− patients demonstrated a significantly worse prognosis than N0/RHAMM+/TIL− patients (P=0.005). Loss of CD8+ TILs was predictive of local recurrence in RHAMM+ tumours (P=0.009) only. RHAMM and CD8+ TILs may assist in identifying early stage rectal cancer patients facing a particularly poor prognosis and who may derive a benefit from preoperative therapy.
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影响因子：
45.3
作者：
Mohiuddin, M;Winter, K;Willett, C
通讯作者：
Willett, C
影响因子：
11.5
作者：
Zlobec, Inti;Baker, Kristi;Lugli, Alessandro
通讯作者：
Lugli, Alessandro
影响因子：
11.5
作者：
Zlobec, Inti;Terracciano, Luigi M.;Lugli, Alessandro
通讯作者：
Lugli, Alessandro
影响因子：
45.3
作者：
Guillem, Jose G.;Diaz-Gonzalez, Juan A.;Pucciarelli, Salvatore
通讯作者：
Pucciarelli, Salvatore
影响因子：
3.9
作者：
Kyzer, S;Gordon, PH
通讯作者：
Gordon, PH