Kittl E M, Ruckser R, Selleny S, Samek V, Hofmann J, Huber K, Reiner A, Ogris E, Hinterberger W, Bauer K
Institute of Laboratory Medicine Donauspital, Vienna, Austria.
Exp Clin Immunogenet. 1997;14(4):264-72.
Aberrant expression of CD44 splice variants has been detected on a variety of human tumor cells. Overexpression of specific isoforms has been shown to be associated with metastasis and poor prognosis in breast cancer. We evaluated the possible utility of soluble CD44 splice variant v5 (sCD44v5) as a circulating, tumor-associated marker in breast cancer patients. Serum levels of sCD44v5 were determined in 147 healthy volunteers, in 53 patients with nonmalignant breast disease, in 85 patients with breast cancer at presentation, in 13 patients with recurrence and in 73 patients with active metastatic disease. Statistically, the levels at presentation in stages I-IV, in benign disease, and in a female control group were not significantly different. First longitudinal studies over 1-2 years in the follow-up of 28 patients who have remained tumor-free showed considerable between-patient variation while the intrapatient levels remained within relatively narrow limits. In patients with active metastatic disease, elevated levels of sCD44v5 (> 58 ng.ml-1) were detected in 50% of the cases with marked elevation in only 26%. In these cases, sCD44v5 correlated with the extent of metastatic disease and fell during clinical response to cytoreductive therapy. In comparison with CA15-3 in the patients' follow-up serum levels of sCD44v5 proved to be much less sensitive concerning lead time, percentage of raised serum levels at the time of recurrence and in metastatic disease. The value of sCD44v5 determinations in breast cancer patients was further limited by the poor diagnostic specificity of this marker due to elevated levels in smokers and chronic inflammatory disease.
在多种人类肿瘤细胞上已检测到CD44剪接变体的异常表达。特定异构体的过表达已被证明与乳腺癌的转移和不良预后相关。我们评估了可溶性CD44剪接变体v5（sCD44v5）作为乳腺癌患者循环肿瘤相关标志物的潜在用途。测定了147名健康志愿者、53名非恶性乳腺疾病患者、85名初诊乳腺癌患者、13名复发患者和73名有活跃转移疾病患者的血清sCD44v5水平。从统计学上看，I-IV期、良性疾病患者以及女性对照组的初诊水平无显著差异。对28名无瘤患者进行的为期1-2年的首次纵向研究表明，患者之间存在相当大的差异，而患者体内水平保持在相对狭窄的范围内。在有活跃转移疾病的患者中，50%的病例检测到sCD44v5水平升高（>58 ng.ml-1），其中仅有26%显著升高。在这些病例中，sCD44v5与转移疾病的程度相关，并且在细胞减灭治疗的临床反应期间下降。在患者随访中，与CA15-3相比，sCD44v5的血清水平在提前期、复发时和转移疾病时血清水平升高的百分比方面敏感性要低得多。由于吸烟者和慢性炎症性疾病患者中该标志物水平升高，导致其诊断特异性较差，这进一步限制了sCD44v5检测在乳腺癌患者中的价值。
