Cytoplasmic Trop-1/Ep-CAM Overexpression is Associated with a Favorable Outcome in Node-positive Breast Cancer
Cytoplasmic Trop-1/Ep-CAM Overexpression is Associated with a Favorable Outcome in Node-positive Breast Cancer
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DOI：
10.1093/jjco/hys159
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发表时间：
2012-12-01
影响因子：
2.4
通讯作者：
Coradini, Danila
中科院分区：
文献类型：
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作者：
Alberti, Saverio;Ambrogi, Federico;Coradini, Danila
Trop-1/Ep-CAM 调节转化细胞的生长和存活，在包括乳腺癌在内的大多数癌症中高度表达。在评估肿瘤细胞中的 Trop-1/上皮细胞粘附分子 (Ep-CAM) 表达时，通常只考虑膜染色。然而，有证据表明 Trop-1/Ep-CAM 作为功能无能的分子保留在细胞质内囊泡中。因此，我们研究了细胞质免疫染色相对于膜染色是否具有独立的临床意义。在中位随访 99 个月的 642 例单侧乳腺癌患者中，对膜和细胞质 Trop-1/Ep-CAM 表达进行了免疫组织化学研究。使用多重对应分析来研究 Trop-1/Ep-CAM 与其他生物变量之间的关联。 Trop-1/Ep-CAM 表达对患者预后的影响通过 KaplanMeier 方法和比例风险 Cox 模型评估为无事件生存。虽然具有中度/强膜染色的肿瘤大多与伴随的细胞质 Trop-1/Ep-CAM 表达相关 (97)，但具有弱至零膜染色的肿瘤在 23 例中显示出中/高细胞质表达。无论接受何种辅助治疗，细胞质过度表达都与良好的结果相关，尤其是在淋巴结阳性患者中。Trop-1/Ep-CAM 表达根据其亚细胞定位可能具有不同的临床意义。
Trop-1/Ep-CAM modulates growth and survival of transformed cells, and it is highly expressed in most carcinomas including breast cancer. Only membranous staining is typically considered in evaluating Trop-1/epithelial cell adhesion molecule (Ep-CAM) expression in tumor cells. However, there is evidence of retention of Trop-1/Ep-CAM, as functionally incompetent molecules, in intra-cytoplasmic vesicles. Hence, we investigated whether cytoplasmic immunostaining may have an independent clinical significance with respect to membranous staining.Membranous and cytoplasmic Trop-1/Ep-CAM expression was immunohistochemically investigated in 642 unilateral breast cancers from patients with a 99-month median follow-up. Multiple correspondence analysis was used to investigate the association between Trop-1/Ep-CAM and other biological variables. The impact of Trop-1/Ep-CAM expression on the patients outcome was evaluated as event-free survival by the KaplanMeier method and proportional hazard Cox model.While tumors with intermediate/strong membranous staining were mostly associated with concomitant cytoplasmic Trop-1/Ep-CAM expression (97), tumors with weak-to-nil membranous staining showed intermediate/high cytoplasmic expression in 23 of cases. Cytoplasmic overexpression was associated with a favorable outcome, especially in node-positive patients, regardless of the adjuvant therapy received.Trop-1/Ep-CAM expression may have different clinical implications according to its subcellular localization.