The prognostic value of
hyaluronan (HA) was analyzed in a large number of patients (n = 261) with
non-small-cell lung cancer (NSCLC) by staining archived
tumor samples with a biotinylated HA-specific probe. The level of HA in the
tumor cells and surrounding stroma was scored and compared with parallel CD44 stainings, clinicopathological factors and survival data.
Adenocarcinomas were characterized by a low percentage of HA-positive cells with low staining intensity compared with squamous-cell and large-cell/
anaplastic carcinomas. The HA signal in the peri-tumoral stroma was often higher than that in the uninvolved stroma in all subgroups of NSCLC. CD44 and HA associated with the
cancer cells showed a strong positive correlation with each other. 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
adenocarcinoma subgroup was the 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 survival (DFS) together with stage and
tumor type. However, in the subgroup of patients with
adenocarcinoma (n = 49), a strong stromal signal for HA predicted poor DFS. The level of HA in the stroma of
adenocarcinomas retained its prognostic value in Cox's multivariate analysis. These results indicate that the frequency and intensity of HA has a significant prognostic value in NSCLC, particularly when the histological subtypes are analyzed as separate entities.