Campo Leticia, Turley Helen, Han Cheng, Pezzella Francesco, Gatter Kevin C, Harris Adrian L, Fox Stephen B
Nuffield Department Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK.
J Pathol. 2005 Apr;205(5):585-91. doi: 10.1002/path.1740.
Angiogenin, a 14.2 kD polypeptide that was originally noted for its angiogenic activity, is now increasingly recognized to have a multiplicity of biological roles in both physiological and pathological conditions. In breast cancer, there are conflicting studies questioning the role of angiogenin. Here, the pattern of expression of angiogenin during the transition from normal breast tissue to ductal carcinoma in situ and invasive carcinoma is reported together with the correlates between the level of angiogenin in 239 invasive carcinomas and standard clinicopathological parameters, hypoxia-inducible factor (HIF)-1 alpha and the HIF-1 alpha target gene DEC-1. This study shows that angiogenin expression is up-regulated in the cytoplasmic and nuclear compartments in in situ carcinoma and invasive carcinoma compared with normal breast tissue and that angiogenin expression in invasive carcinomas is significantly positively associated with high tumour grade (p = 0.03), positive oestrogen receptor (ER) status (p = 0.01), HIF-1 alpha (p = 0.001) and DEC 1 (p = 0.001), but not with patient age (p = 0.8), tumour size (p = 0.25), lymph node status (p = 0.69), epidermal growth factor receptor (p = 0.56) or microvessel density (p = 0.32). No difference in relapse-free (p = 0.26) or overall (p = 0.63) survival was observed in patients stratified by angiogenin expression. This study suggests that angiogenin may be important in breast cancer progression and that, through its relationship with ER, it may be a target for tamoxifen.
血管生成素是一种14.2 kD的多肽,最初因其血管生成活性而受到关注,现在人们越来越认识到它在生理和病理条件下具有多种生物学作用。在乳腺癌中,关于血管生成素作用的研究结果相互矛盾。在此,我们报告了血管生成素在从正常乳腺组织向导管原位癌和浸润性癌转变过程中的表达模式,以及239例浸润性癌中血管生成素水平与标准临床病理参数、缺氧诱导因子(HIF)-1α和HIF-1α靶基因DEC-1之间的相关性。本研究表明,与正常乳腺组织相比,原位癌和浸润性癌中血管生成素在细胞质和细胞核中的表达上调,且浸润性癌中血管生成素的表达与高肿瘤分级(p = 0.03)、雌激素受体(ER)阳性状态(p = 0.01)、HIF-1α(p = 0.001)和DEC 1(p = 0.001)显著正相关,但与患者年龄(p = 0.8)、肿瘤大小(p = 0.25)、淋巴结状态(p = 0.69)、表皮生长因子受体(p = 0.56)或微血管密度(p = 0.32)无关。根据血管生成素表达分层的患者在无复发生存率(p = 0.26)或总生存率(p = 0.63)方面未观察到差异。本研究提示血管生成素可能在乳腺癌进展中起重要作用,并且通过其与ER的关系,它可能是他莫昔芬的一个作用靶点。