转化生长因子-β结合受体内皮糖蛋白（CD105）在食管癌及癌旁非肿瘤性食管组织中的表达作为复发的预后预测指标

Transforming growth factor-beta binding receptor endoglin (CD105) expression in esophageal cancer and in adjacent nontumorous esophagus as prognostic predictor of recurrence.

作者信息

Bellone Graziella, Solerio Dino, Chiusa Luigi, Brondino Gabriele, Carbone Anna, Prati Adriana, Scirelli Tiziana, Camandona Michele, Palestro Giorgio, Dei Poli Marcello

机构信息

Division of Internal Medicine, Department of Clinical Physiopathology, University of Turin, Turin, Italy.

出版信息

Ann Surg Oncol. 2007 Nov;14(11):3232-42. doi: 10.1245/s10434-007-9528-z. Epub 2007 Aug 8.

DOI:10.1245/s10434-007-9528-z

PMID:17682823

Abstract

BACKGROUND

We hypothesized that the potent neovascularization marker endoglin (CD105), by differentially highlighting a subset of microvessels (MV) in esophageal cancer (EC), could provide better prognostic/therapeutic information than the panendothelial marker CD34, which also highlights MV.

METHODS

Endoglin messenger ribonucleic acid (mRNA) expression in normal, malignant, and adjacent nontumorous esophagus tissue was quantified by real-time reverse-transcription polymerase chain reaction (RT-PCR). Sections of formalin-fixed, paraffin-embedded tissues were analyzed immunohistochemically for CD105 and CD34. MV density was counted following a standard protocol. Circulating soluble endoglin levels were determined in patient and control sera, and compared with clinical outcome.

RESULTS

CD105 mRNA was upregulated by a median factor of 2.89 in ECs versus controls. In 28% of patients, CD105 mRNA was upregulated by a median factor of 2.65 in adjacent non-tumorous versus normal tissue. In tumor tissues, CD105 was stained negatively or positively only in a subset of MV. CD34 always showed positive extensive MV staining. In adjacent nontumorous esophagus, CD105 rarely showed diffuse MV staining, while CD34 stained blood-vessel endothelial cells in all non-neoplastic tissue. CD105 expression was high in residual highly dysplastic Barrett's-type mucosa associated with some adenocarcinomas. No statistically significant difference in endoglin serum levels appeared between patients and normal subjects. Correlation with clinicopathological data showed higher intra-tumor MV-CD105+ scores at more-advanced clinical stages. High-scoring MV-CD105+ patients had significantly shorter disease-free and overall survival; MV-CD34+ density was not survival related. Diffuse CD105 expression in adjacent nontumorous esophagus predicted poorer disease-free and overall survival.

CONCLUSIONS

Our findings could help identify EC patients who may benefit from targeted anti-angiogenic therapies.

摘要

背景

我们假设，强效的血管生成标志物内皮糖蛋白（CD105）通过特异性地突出显示食管癌（EC）中的一部分微血管（MV），相比于同样能突出显示MV的全内皮标志物CD34，能够提供更好的预后/治疗信息。

方法

通过实时逆转录聚合酶链反应（RT-PCR）对正常、恶性及相邻非肿瘤性食管组织中的内皮糖蛋白信使核糖核酸（mRNA）表达进行定量。对福尔马林固定、石蜡包埋组织切片进行CD105和CD34的免疫组织化学分析。按照标准方案计数MV密度。测定患者和对照血清中循环可溶性内皮糖蛋白水平，并与临床结果进行比较。

结果

与对照相比，EC中CD105 mRNA上调，中位数为2.89倍。在28%的患者中，相邻非肿瘤组织中CD105 mRNA上调，中位数为2.65倍。在肿瘤组织中，CD105仅在一部分MV中呈阴性或阳性染色。CD34总是显示广泛的MV阳性染色。在相邻非肿瘤性食管中，CD105很少显示弥漫性MV染色，而CD34在所有非肿瘤组织中均对血管内皮细胞进行染色。与一些腺癌相关的残留高度发育异常的巴雷特型黏膜中CD105表达较高。患者与正常受试者之间内皮糖蛋白血清水平无统计学显著差异。与临床病理数据的相关性显示，在更晚期临床阶段肿瘤内MV-CD105+评分更高。MV-CD105+评分高的患者无病生存期和总生存期显著缩短；MV-CD34+密度与生存期无关。相邻非肿瘤性食管中弥漫性CD105表达预示无病生存期和总生存期较差。