IMMUNOHISTOCHEMICAL ASSESSMENT OF INDIVIDUAL TUMOR-CELLS IN LYMPH-NODES OF PATIENTS WITH NON-SMALL-CELL LUNG-CANCER

Purpose: This prospective study was designed to evaluate the prognosti c relevance and biologic characteristics of a minimal lymphatic tumor load in non-small-cell lung cancer (NSCLC). Methods: Frozen-tissue sec tions from 391 regional lymph nodes of 72 patients with completely res ected NSCLCs, who were staged as free of metastases (pT13,pNO,MO,RO) b y clinical tumor staging procedures and histopathologic examinations, were studied. For tumor-cell detection, we applied the alkaline phosph atase-antialkaline phosphatase (APAAP) immunostaining technique with m onoclonal antibody Ber-Ep4 against two glycoproteins of 34 and 49 kd p resent of the surface and cytoplasm of epithelial cells. Results: Indi vidual Ber-Ep4-positive cells were de tected in 11 of 72 (15.2%) cance r patients, while positive staining was consistently absent in all sec tions from control nodes of 24 noncarcinoma patients. No correlation b etween a positive lymph node finding and either the size or differenti ation grade of the primary tumor or the presence of micrometastatic ru mor cells in bone marrow assessed by immunocytochemistry with antikera tin monoclonal antibody CK2 was observed. Following a median observati on time of 26.0 months (range, 15 to 39), patients with lymph node mic rometastases showed a significantly shorter disease-free survival dura tion than node-negative patients (log-rank test, P = .005). The indepe ndence of this prognostic significance was demonstrated by a multivari ate analysis (Cox regression model, P = .005). Conclusion: 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 micr ometastases in lymph nodes is recommended for current tumor staging in NSCLC, as it might lead to better stratification of patients for adju vant therapy. (C) 1994 by American Society of Cliniccll Oncology.