摘要
三阴性乳腺癌是乳腺癌一种特殊分子亚型,雌激素受体(estrogen receptor,ER)、孕激素受体(progesteronereceptor,PR)和HER均不表达。它是一种异质性肿瘤,不仅表现在分子水平上,而且在病理和临床方面都具有异质性。三阴性乳腺癌可以进一步分为基底细胞样型和非基底样型两个亚型,基底细胞样型免疫组织化学表达EGFR和/或CK5/6,大多数三阴性乳腺癌是基底细胞样型。三阴性乳腺癌与非三阴性乳腺癌比较,通常更具侵袭性,预后差,缺乏有针对性的分子靶向治疗,因此这型肿瘤治疗困难。改善此型肿瘤预后的关键是开发新的、有效的治疗策略。本文综述了最近用免疫组织化学方法对三阴性乳腺癌患者预后和预测很有价值的一系列(5个)肿瘤标志物的研究。三阴性乳腺癌中Ki67和p53的表达常常明显升高,这与肿瘤激素受体呈阴性有关,而与HER2的阴性表达无关。Ki67的表达水平高(>10%)明显与三阴性乳腺癌淋巴结转移相关,Ki67比p53有更好的预测价值。在雄激素受体(androgen receptor,AR)表达的三阴性乳腺癌中,降低的AR表达与远处转移相关,且AR和Ki67表达呈明显的负相关。同未转移者比较,伴有淋巴结转移和远处转移的基底细胞样亚型三阴性乳腺癌与瘤体内EGFR和CK5/6高表达显著相关。因此,不是其表达频率,而是瘤体内EGFR和CK5/6表达增高、AR表达降低可能在转移中发挥作用,可以预测三阴性乳腺癌远处转移。抗EGFR和抗AR的靶向治疗可能是三阴性乳腺癌潜在的治疗选择,尤其是对常规化疗无效者。
Triple-negative（TN） carcinoma is a molecular subtype of breast cancer characterized by the lack of expression of estrogen receptor（ER）,progesterone receptor（PR） and HER-2.It is a heterogeneous disease,not only on the molecular level,but also on the pathologic and clinical aspects.TN tumors can be further classified into two subtypes： basal-like,defined as expressing epidermal growth factor receptor（EGFR） and / or cytokeratin（CK） 5 /6 by immunohistochemistry,and non-basal-like;the majority of TN tumors are basal-like.TN tumors usually have a more aggressive behaviour and poorer outcome compared with non-TN breast cancers,and lack molecular targets commonly used in targeted therapy,making this group of tumors difficult to treat.Developing novel,effective treatment strategies for these tumors is crucial for improving their prognosis.This review describes a recent study series on prognostic and predictive values of tumor biomarker susing in TN breast cancer patients.TN tumors are associated with significantly higher expression of Ki67 and p53 compared to non-TN tumors.Hormone receptor negativity rather than HER-2 negativity is associated with the increased Ki67 and p53 expression in TN tumors.Furthermore,high expression level of Ki67（ 10%） but not p53,is significantly associated with nodal metastasis in TN tumors,indicating that Ki67 has better prognostic value than p53.TN tumors with distant metastases are significantly associated with lower expression of androgen receptor（AR） as compared to those with only loco-regional disease;there is a significant negative correlation between AR and Ki67 expressions among AR expressing TN tumors.Basal-like subtype TN tumors with nodal and distant metastases are associated with significantly higher intratumoral expression of EGFR and CK5 /6 as compared to those without metastases.Therefore,increased EGFR and CK5 /6 intratumoral expression and decreased AR intratumoral expression,rather than the frequency of their expression,may play a role in the development of metastases and may be predictive of metastatic disease in TN breast cancer patients.Anti-EGFR and anti-AR targeted therapies may provide potential treatment options for TN carcinomas,especially those tumors not responding to chemotherapy.
出处
《北京大学学报（医学版）》
CAS
CSCD
北大核心
2012年第5期666-672,共7页
Journal of Peking University:Health Sciences
关键词
乳腺肿瘤
肿瘤标记
生物学
受体
表皮生长因子
受体
雄激素
Breast neoplasms
Tumor markers
biological
Receptor
epidermal growth factor
Receptor
androgen
