Passlick B, Izbicki J R, Kubuschok B, Nathrath W, Thetter O, Pichlmeier U, Schweiberer L, Riethmüller G, Pantel K
Department of Surgery, Klinikum Innenstadt, Ludwig-Maximilians-Universität, Munich, Germany.
J Clin Oncol. 1994 Sep;12(9):1827-32. doi: 10.1200/JCO.1994.12.9.1827.
This prospective study was designed to evaluate the prognostic relevance and biologic characteristics of a minimal lymphatic tumor load in non-small-cell lung cancer (NSCLC).
Frozen-tissue sections from 391 regional lymph nodes of 72 patients with completely resected NSCLCs, who were staged as free of metastases (pT1-3, pN0,M0,R0) by clinical tumor staging procedures and histopathologic examinations, were studied. For tumor-cell detection, we applied the alkaline phosphatase-antialkaline phosphatase (APAAP) immunostaining technique with monoclonal antibody Ber-Ep4 against two glycoproteins of 34 and 49 kd present of the surface and cytoplasm of epithelial cells.
Individual Ber-Ep4-positive cells were detected in 11 of 72 (15.2%) cancer patients, while positive staining was consistently absent in all sections from control nodes of 24 noncarcinoma patients. No correlation between a positive lymph node finding and either the size or differentiation grade of the primary tumor or the presence of micrometastatic tumor cells in bone marrow assessed by immunocytochemistry with antikeratin monoclonal antibody CK2 was observed. Following a median observation time of 26.0 months (range, 15 to 39), patients with lymph node micrometastases showed a significantly shorter disease-free survival duration than node-negative patients (log-rank test, P = .005). The independence of this prognostic significance was demonstrated by a multivariate analysis (Cox regression model, P = .005).
Our results provide evidence that the presence of single lung carcinoma cells in lymph nodes is an independent indicator of the disseminatory capacity of an individual primary tumor. Immunohistochemical assessment of micrometastases in lymph nodes is recommended for current tumor staging in NSCLC, as it might lead to better stratification of patients for adjuvant therapy.
本前瞻性研究旨在评估非小细胞肺癌（NSCLC）中微小淋巴肿瘤负荷的预后相关性和生物学特性。
对72例完全切除的NSCLC患者的391个区域淋巴结的冰冻组织切片进行研究，这些患者经临床肿瘤分期程序和组织病理学检查分期为无转移（pT1 - 3，pN0，M0，R0）。为检测肿瘤细胞，我们应用碱性磷酸酶 - 抗碱性磷酸酶（APAAP）免疫染色技术，使用针对上皮细胞表面和细胞质中存在的34和49 kd两种糖蛋白的单克隆抗体Ber - Ep4。
72例癌症患者中有11例（15.2%）检测到单个Ber - Ep4阳性细胞，而24例非癌患者的对照淋巴结所有切片中均未出现阳性染色。未观察到阳性淋巴结发现与原发肿瘤的大小或分化程度，或通过抗角蛋白单克隆抗体CK2免疫细胞化学评估的骨髓中微转移肿瘤细胞的存在之间存在相关性。在中位观察时间为26.0个月（范围15至39个月）后，有淋巴结微转移的患者无病生存期明显短于淋巴结阴性患者（对数秩检验，P = 0.005）。多变量分析（Cox回归模型，P = 0.005）证明了这种预后意义的独立性。
我们的结果表明，淋巴结中单个肺癌细胞的存在是个体原发肿瘤播散能力的独立指标。建议对NSCLC进行当前肿瘤分期时对淋巴结微转移进行免疫组织化学评估，因为这可能导致患者辅助治疗的更好分层。
