Leavey Patrick J, Timmons Charles, Frawley William, Lombardi Donald, Ashfaq Raheela
Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9063, USA.
Pediatr Dev Pathol. 2006 May-Jun;9(3):219-24. doi: 10.2350/11-05-0137.1.
Recent evidence implicates cell surface proteins of the tetraspanin superfamily in the process of metastasis whereas the downregulation of KAI-1, a member of the tetraspanin family, is associated with an aggressive clinical phenotype in several types of human cancers. To determine if expression of KAI-1-1 is associated with any known prognostic marker or clinical outcome in high-grade osteosarcoma, we examined 91 nondecalcified archival samples from 47 patients for the expression of KAI-1. Archival, paraffin-embedded, and decalcified pathologic samples were examined by immunohistochemistry and results were correlated to clinical outcomes and known prognostic markers. There were 46 samples from diagnostic biopsies (1 diagnostic sample was not available), 32 tumor resection samples, and 13 metastasis samples. Thirty-three percent (n=30) of the samples expressed KAI-1 (16 biopsies, 9 resections, and 5 metastasis). KAI-1 expression was not significantly related to known prognostic markers or to either tumor necrosis after neoadjuvant therapy or the incidence of metastasis at diagnosis. KAI-1 expression was not significantly different between paired diagnostic tumor samples and either resection or metastasis tumor samples. Twenty-five patients remain alive at a median follow-up of 95 months. The overall and progression-free survival percentages at 5 years were 62% and 47% for KAI-1-positive patients and 49% and 38% for KAI-1-negative patients, respectively. This difference was not statistically significant. We conclude that KAI-1 is expressed in a proportion of high-grade osteosarcoma but is not of clinical significance and cannot be used to stratify treatment groups for these patients.
最近有证据表明,四跨膜蛋白超家族的细胞表面蛋白参与了转移过程,而四跨膜蛋白家族成员KAI-1的下调与多种人类癌症的侵袭性临床表型相关。为了确定KAI-1-1的表达是否与高级别骨肉瘤的任何已知预后标志物或临床结果相关,我们检查了来自47例患者的91份非脱钙存档样本中KAI-1的表达情况。通过免疫组织化学检查存档的、石蜡包埋的和脱钙的病理样本,并将结果与临床结果和已知预后标志物进行关联。其中有46份诊断性活检样本(1份诊断样本无法获取)、32份肿瘤切除样本和13份转移样本。33%(n=30)的样本表达KAI-1(16份活检样本、9份切除样本和5份转移样本)。KAI-1的表达与已知预后标志物、新辅助治疗后的肿瘤坏死情况或诊断时的转移发生率均无显著相关性。配对的诊断性肿瘤样本与切除或转移肿瘤样本之间的KAI-1表达无显著差异。25例患者在中位随访95个月时仍存活。KAI-1阳性患者5年的总生存率和无进展生存率分别为62%和47%,KAI-1阴性患者分别为49%和38%。这种差异无统计学意义。我们得出结论,KAI-1在一部分高级别骨肉瘤中表达,但不具有临床意义,不能用于对这些患者的治疗组进行分层。