Anttila M A, Tammi R H, Tammi M I, Syrjänen K J, Saarikoski S V, Kosma V M
Department of Obstetrics and Gynecology, University of Kuopio, Finland.
Cancer Res. 2000 Jan 1;60(1):150-5.
Several malignant tumors accumulate hyaluronan, a matrix component suggested to promote cancer cell migration and growth. To explore the potential clinical importance of this concept, we assessed the hyaluronan levels in epithelial ovarian cancer. A biotinylated affinity probe specific for hyaluronan was prepared and applied to histological sections of 309 epithelial ovarian cancers and 45 matched metastatic lesions. The staining was scored according to the percentage area of strong hyaluronan signal of total peri- and intratumoral stroma as low (<35%), moderate (35-75%), or high (>75%). Low, moderate, and high levels of stromal hyaluronan were observed in 95, 116, and 98 carcinomas, respectively. The high stromal hyaluronan level was significantly associated with poor differentiation, serous histological type, advanced stage, and large primary residual tumor, whereas it was not correlated with high CD44 expression on cancer cells. The 5-year outlook of the disease deteriorated with increasing stromal hyaluronan levels for both overall (45% versus 39% versus 26%; P = 0.002) and recurrence-free (66% versus 56% versus 40%; P = 0.008) survival. High levels of stromal hyaluronan were more frequent in metastatic lesions than in primary tumors (z = -3.9; P = 0.0001). In Cox's multivariate analyses, high level of stromal hyaluronan was an independent prognostic factor in all patients, as well as in stage-specific subgroups. These results suggest that stromal hyaluronan accumulation may be a powerful enhancer of tumor progression and, as such, provides a novel, independent prognostic marker and a potential target of therapy.
几种恶性肿瘤会积聚透明质酸，这是一种被认为可促进癌细胞迁移和生长的基质成分。为了探究这一概念潜在的临床重要性，我们评估了上皮性卵巢癌中的透明质酸水平。制备了一种对透明质酸具有特异性的生物素化亲和探针，并将其应用于309例上皮性卵巢癌和45例匹配的转移灶的组织切片。根据肿瘤周围和肿瘤内基质中透明质酸强信号占总基质面积的百分比，将染色分为低（<35%）、中（35 - 75%）、高（>75%）三个等级。在95例、116例和98例癌组织中分别观察到低、中、高基质透明质酸水平。高基质透明质酸水平与低分化、浆液性组织学类型、晚期和大的原发残留肿瘤显著相关，而与癌细胞上高CD44表达无关。总体生存率（45%对39%对26%；P = 0.002）和无复发生存率（66%对56%对40%；P = 0.008）均随着基质透明质酸水平升高而恶化。转移灶中高基质透明质酸水平比原发肿瘤更常见（z = -3.9；P = 0.0001）。在Cox多因素分析中，高基质透明质酸水平在所有患者以及特定分期亚组中都是独立的预后因素。这些结果表明，基质透明质酸积聚可能是肿瘤进展的有力促进因素，因此，它提供了一种新的、独立的预后标志物和潜在的治疗靶点。
