NEUTROPHIL ALVEOLITIS IN BRONCHIOLOALVEOLAR CARCINOMA - INDUCTION BY TUMOR-DERIVED INTERLEUKIN-8 AND RELATION TO CLINICAL OUTCOME

Tumor infiltrate, predominantly constituted by lymphocytes, may repres ent an important prognostic factor in bronchioloalveolar carcinoma (BA C), in addition to tumor extension and histological type. In the prese nt study, we determined the presence, the origin, and the prognostic i mportance of neutrophils that also participate in leukocyte infiltrate s of BAG. Neutrophil alveolitis was determined immunohistochemically i n both lung biopsies and bronchoalveolar lavage (BAL) fluid samples fr om 29 patients with histologically proved BAG. The local expression of interleukin (IL)-8 was determined by immunohistochemical and immunoen zymatic techniques, Neutrophil counts were analyzed in relation to the clinical outcome of patients by the Kaplan-Meier method and Cox's uni variate and stepwise multivariate models, Lymphocytes and neutrophils dominated the inflammatory cell population in the lower respiratory tr act of patients with BAG. Neutrophils were located mainly in the alveo lar lumen and seldom in alveolar wall whereas lymphocytes were exclusi vely present in alveolar wall, A relationship was observed between the number of neutrophils and the level of IL-8 in BAL fluid suggesting t he involvement of that chemokine in neutrophil recruitment, The tumor cells were the predominant cells that appeared to express IL-8 by immu nolocalization. The presence of increased numbers of neutrophils was s ignificantly associated with a poorer outcome in patients with BAC (P = 0.02). In a multivariate analysis, the neutrophil percentage in BAL fluid was an independent predictor of clinical outcome. The risk of de ath was increased substantially (rate ratio, 5.2; 95% confidence inter val, 1.1 to 24.7) among patients with BAL neutrophil percentage of gre ater than or equal to 39% (median of the distribution) as compared wit h the others, In BAG, neutrophils accumulate in the alveolar lumen, El aboration of IL-8 by tumor cells may be responsible for this event, wh ich is associated with a significantly higher risk of death.