Pirinen R, Tammi R, Tammi M, Hirvikoski P, Parkkinen J J, Johansson R, Böhm J, Hollmén S, Kosma V M
Department of Pathology and Forensic Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, Finland.
Int J Cancer. 2001 Jan 20;95(1):12-7. doi: 10.1002/1097-0215(20010120)95:1<12::aid-ijc1002>3.0.co;2-e.
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.
通过使用生物素化的透明质酸（HA）特异性探针染色存档的肿瘤样本，分析了大量非小细胞肺癌（NSCLC）患者（n = 261）中HA的预后价值。对肿瘤细胞和周围基质中HA的水平进行评分，并与平行的CD44染色、临床病理因素和生存数据进行比较。与鳞状细胞癌和大细胞/间变性癌相比，腺癌的特点是HA阳性细胞百分比低且染色强度低。在NSCLC的所有亚组中，肿瘤周围基质中的HA信号通常高于未受累基质中的信号。与癌细胞相关的CD44和HA彼此呈强正相关。在以鳞状细胞癌为主（n = 168）的整个肿瘤材料中，癌细胞相关HA百分比低的病例中更常发现复发。然而，在腺癌亚组（n = 68）中，细胞相关HA的高百分比与肿瘤低分化相关。基质HA信号强的腺癌病例中复发数量增加也是腺癌亚组的特异性表现。在整个材料（n = 189）的生存分析中，HA阳性癌细胞的低百分比与无病生存期（DFS）缩短以及分期和肿瘤类型相关。然而，在腺癌患者亚组（n = 49）中，HA的强基质信号预示着DFS不良。在Cox多变量分析中，腺癌基质中HA的水平保留了其预后价值。这些结果表明，HA的频率和强度在NSCLC中具有显著的预后价值，特别是当将组织学亚型作为单独实体进行分析时。
