Prognostic value of hyaluronan expression in non-small-cell lung cancer: Increased stromal expression indicates unfavorable outcome in patients with adenocarcinoma

The prognostic value of hyaluronan (HA) was analyzed in a large number of p atients (n = 261) with non-small-cell lung cancer (NSCLC) by staining archi ved tumor samples with a biotinylated HA-specific probe. The level of HA in the tumor cells and surrounding stroma was scored and compared with parall el CD44 stainings, clinicopathological factors and survival data. Adenocarc inomas were characterized by a low percentage of HA-positive cells with low staining intensity compared with squamous-cell and large-cell/anaplastic c arcinomas. The HA signal in the peri-tumoral stroma was often higher than t hat in the uninvolved stroma in all subgroups of NSCLC, CD44 and HA associa ted with the cancer cells showed a strong positive correlation with each ot her. In the whole tumor material, dominated by squamous-cell carcinomas (n = 168), recurrences were more often found in cases showing a low percentage of cancer cell-associated HA. However, within the adenocarcinoma subgroup (n = 68), a high percentage of cell-associated HA was correlated with poor tumor differentiation. Also specific for the adenocavcinoma subgroup was th e increased number of recurrences in cases with a strong stromal HA signal. In survival analysis of the whole material (n = 189), a low percentage of HA-positive cancer cells was associated with a shortened disease-free survi val (DFS) together with stage and tumor type. However, in the subgroup of p atients with adenocarcinoma (n = 49), a strong stromal signal for HA predic ted poor DFS, The level of HA in the stroma of adenocarcinomas retained its prognostic value in Cox's multivariate analysis. These results indicate th at the frequency and intensity of HA has a significant prognostic value in NSCLC, particularly when the histological subtypes are analyzed as separate entities. (C) 2001 Wiley-Liss, Inc.