黏液表达对接受辅助化疗的可切除非小细胞肺癌患者预后意义的交叉验证分析：来自 IALT、JBR.10 和 ANITA 的结果。
Cross-validation analysis of the prognostic significance of mucin expression in patients with resected non-small cell lung cancer treated with adjuvant chemotherapy: results from IALT, JBR.10 and ANITA.
机构信息
Department of Medicine, State University of New York Upstate Medical University, Syracuse, NY, USA(2).
出版信息
Lung Cancer. 2013 Oct;82(1):149-55. doi: 10.1016/j.lungcan.2013.06.015. Epub 2013 Aug 4.
INTRODUCTION
CALGB 9633 was a randomized trial of observation versus adjuvant chemotherapy for patients with stage IB non-small cell lung cancer (NSCLC). In CALGB 9633, the presence of mucin in the primary tumor was associated with shorter disease-free survival (DFS; hazard ratio (HR) = 1.9, p = 0.002) and overall survival (OS; HR = 1.9, p = 0.004).
METHODS
To validate these results, mucin staining was performed on primary tumor specimens from 780 patients treated on IALT, 351 on JBR.10 and 150 on ANITA. The histochemical technique using mucicarmine was performed. The prognostic value of mucin for DFS and OS was tested in a Cox model stratified by trial and adjusted for clinical and pathological factors. A pooled analysis of all 4 trials was performed for the predictive value of mucin for benefit from adjuvant chemotherapy.
RESULTS
The cross-validation group had 48% squamous, 37% adenocarcinoma and 15% other NSCLC compared with 29%, 56%, and 15%, respectively in CALGB. Among 1262 patients with assessable results, mucin was positive in IALT 24%, JBR.10 30%, ANITA 22% compared with 45% in CALGB. Histology was the only significant covariate (p < 0.0001) in multivariate analysis with mucin seen more commonly in adenocarcinoma (56%) compared with squamous (5%) and other NSCLC (15%). Mucin was a borderline negative prognostic factor for DFS (HR = 1.2 [1.0-1.5], p = 0.06) but not significantly so for OS (HR=1.1 [0.9-1.4], p = 0.25). Prognostic value did not vary according to histology: HR = 1.3 [1.0-1.6] in adenocarcinoma vs. 1.6 [1.2-2.2] for DFS in other histology (interaction p = 0.69). Mucin status was not predictive for benefit from adjuvant chemotherapy (test of interaction: DFS p = 0.27; OS p = 0.49).
CONCLUSIONS
Mucin was less frequent in the cross-validation group due to its higher percentage of squamous cell carcinomas. The negative impact of mucin was confirmed for DFS but not for OS. Mucin expression was not predictive of overall survival benefit from adjuvant chemotherapy.
简介
CALGB 9633 是一项针对 IB 期非小细胞肺癌（NSCLC）患者观察与辅助化疗的随机试验。在 CALGB 9633 中，肿瘤原发灶中存在粘蛋白与无病生存期（DFS；风险比（HR）=1.9，p=0.002）和总生存期（OS；HR=1.9，p=0.004）较短相关。
方法
为了验证这些结果，对 IALT 治疗的 780 例患者、JBR.10 治疗的 351 例患者和 ANITA 治疗的 150 例患者的肿瘤原发灶标本进行了粘蛋白染色。使用粘卡红进行组织化学染色。在按试验分层并调整临床和病理因素的 Cox 模型中，检测粘蛋白对 DFS 和 OS 的预后价值。对所有 4 项试验进行了粘蛋白对辅助化疗获益的预测价值的汇总分析。
结果
在 IALT、JBR.10 和 ANITA 中，交叉验证组中分别有 48%的鳞癌、37%的腺癌和 15%的其他 NSCLC，而在 CALGB 中则分别为 29%、56%和 15%。在可评估结果的 1262 例患者中，ILAT 中粘蛋白阳性率为 24%，JBR.10 为 30%，ANITA 为 22%，而在 CALGB 中则为 45%。在多变量分析中，组织学是唯一具有显著意义的协变量（p<0.0001），粘蛋白在腺癌（56%）中比鳞癌（5%）和其他 NSCLC（15%）更常见。粘蛋白对 DFS 是一个边缘负预后因素（HR=1.2[1.0-1.5]，p=0.06），但对 OS 无显著影响（HR=1.1[0.9-1.4]，p=0.25）。预后价值不因组织学而异：在腺癌中，HR=1.3[1.0-1.6]，在其他组织学中为 1.6[1.2-2.2]（DFS 交互作用 p=0.69）。粘蛋白状态不能预测辅助化疗的获益（交互检验：DFS p=0.27；OS p=0.49）。
结论
交叉验证组中由于鳞癌比例较高，粘蛋白的频率较低。粘蛋白对 DFS 的负面影响得到了确认，但对 OS 无影响。粘蛋白表达不能预测辅助化疗对总生存期的获益。
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