Prognostic Significance of the Metastasis-inducing Protein S 100 A 4 ( p 9 Ka ) in Human Breast Cancer 1
Prognostic Significance of the Metastasis-inducing Protein S 100 A 4 ( p 9 Ka ) in Human Breast Cancer 1
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转移诱导蛋白 S 100 A 4 ( p 9 Ka ) 在人类乳腺癌中的预后意义 1
DOI：
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发表时间：
2000
期刊：
影响因子：
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通讯作者：
R. Barraclough
中科院分区：
文献类型：
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作者：
P. Rudland;A. Platt;C. Renshaw;C. West;J. Winstanley;L. Robertson;R. Barraclough
钙结合蛋白 S100A4 能够在啮齿动物模型中诱导乳腺癌转移。我们现在证明，使用蛋白质印迹技术，重组大鼠 S100A4 的兔抗体可以特异性识别人 S100A4，并使用它们来评估 S100A4 在 1976 年至 1982 年间接受治疗的 349 名 I 期和 II 期乳腺癌患者的原发性肿瘤中的预后意义。该抗体对正常乳腺组织进行异质染色，但对 41% 的癌组织呈阳性染色，其余 59% 呈阴性染色。除了癌细胞外，一些宿主基质细胞和淋巴细胞也被染色，但这些在后续分析中已被忽略。 S100A4 癌染色与一些被认为与患者不良预后相关的肿瘤变量存在关联：腋窝淋巴结中存在的肿瘤（边界 P 5 0.058）、c-erbB-3 染色（P5 0.002）、组织蛋白酶 D（P5 0.024）和 c-erbB-2（P5 0.048）。使用生命表评估了 S100A4 染色与患者生存的关联，并使用广义 Wilcoxon 统计数据进行了分析。 19 年随访后，80% 的 S100A4 阴性患者存活，但只有 11% 的 S100A4 阳性患者存活，且这种相关性非常显着（P<0.0001）；前者的中位生存期>228个月，后者的中位生存期为47个月。其他与生存时间显着相关的肿瘤变量包括淋巴结状态 (P< 0.0001)、肿瘤大小 (P5 0.0035)、组织学分级 (P 5 0.013)、c-erbB-2 染色 (P5 0.0015)、雌激素受体 (P 5 0.028) 和 p53 (P5 0.032)。对 S100A4 染色的癌症患者与由这些其他肿瘤变量定义的亚组中的生存率之间的关联进行的分析表明，在每个亚组中，S100A4 染色与较差的生存率相关。肿瘤染色为 S100A4 并具有受累淋巴结 (P < 0.0001)、固定于胸壁 (P5 0.015) 或染色为 c-erbB-2 (P 5 0.050) 的患者，与仅具有 S100A4 染色肿瘤的患者相比，生存时间显着缩短。 S100A4 阴性组中淋巴结受累或 c-erbB-2 染色的患者并未表现出生存时间的任何显着缩短。对 137 名患者进行的多变量回归分析显示，S100A4 染色与患者死亡的相关性最高 (P < 0.0001)，但受累淋巴结 (P5 0.001)、固定肿瘤 (P 5 0.0002) 和高组织学分级 (P5 0.022) 也是显着的独立预后变量。这些结果表明，在这组患者中，转移诱导蛋白 S100A4 与患者死亡的相关性最为密切。
The calcium-binding protein S100A4 is capable of inducing metastasis in rodent models for breast cancer. We now show that rabbit antibodies to recombinant rat S100A4 recognize specifically human S100A4 using Western blotting techniques and use them to assess the prognostic significance of S100A4 in primary tumors from a group of 349 patients treated between 1976 and 1982 for stage I and stage II breast cancer. The antibody stains normal breast tissue heterogeneously, but stains positively 41% of the carcinomas, leaving the remaining 59% as negatively stained. In addition to the carcinoma cells, some host stromal cells and lymphocytes are also stained, but these have been discounted in subsequent analyses. There is an association of staining of carcinomas for S100A4 with some tumor variables considered to be associated with poor prognosis for patients: tumor present in axillary lymph nodes (borderline P 5 0.058), staining for c-erbB-3 (P5 0.002), cathepsin D (P5 0.024), and c-erbB-2 (P5 0.048). The association of staining for S100A4 with patient survival has been evaluated using life tables and analyzed using generalized Wilcoxon statistics. Eighty percent of the S100A4-negative patients but only 11% of the S100A4-positive patients are alive after 19 years of follow-up, and this association is highly significant (P< 0.0001); the former have a median survival of>228 months and the latter 47 months. The other tumor variables that show significant association with survival time are nodal status (P< 0.0001), tumor size (P5 0.0035), histological grade (P 5 0.013), staining for c-erbB-2 (P5 0.0015), estrogen receptor (P 5 0.028), and p53 (P5 0.032). Analysis of the association of patients with carcinomas staining for S100A4 and their survival in subgroups defined by these other tumor variables shows that in each subgroup, staining for S100A4 is associated with poorer survival. Patients whose tumors stain for S100A4 and possess involved lymph nodes (P < 0.0001), which are fixed to the chest wall (P5 0.015) or which stain for c-erbB-2 (P 5 0.050), show a significant reduction in survival times over those with only S100A4-staining tumors. Patients with involved lymph nodes, or staining for c-erbB-2 in the S100A4-negative group fail to show any significant reduction in survival times. Multivariate regression analysis for 137 patients shows that staining for S100A4 is most highly correlated with patient deaths (P < 0.0001), but involved lymph nodes (P5 0.001), fixed tumors (P 5 0.0002), and high histological grade (P5 0.022) are also significant independent prognostic variables. These results suggest that in this group of patients, the metastasis-inducing protein S100A4 is most tightly correlated with patient demise.
影响因子：
8
作者：
Heide L. Ford;Sayeeda Zain
通讯作者：
Heide L. Ford;Sayeeda Zain