乳腺非典型性导管增生的研究进展

Research progress of breast atypical ductal hyperplasia

乳腺非典型性导管增生(ADH)具有进展为乳腺癌的危险性,ADH的分子生物学及遗传学改变具有一定的特征,与导管原位癌(DCIS)具有一定的相似性。细胞增殖指数的增加、激素受体表达水平升高和细胞生长调节因子等在基因水平上对细胞生长失去正常调控,促进ADH的形成。染色体异常和表观遗传学改变等都可能引发ADH的形成,其中16p、17q染色体异常和肿瘤相关基因启动子区甲基化,可能是ADH形成的早期事件。研究证实,ADH是低级别导管内原位癌(LG-DCIS)的前驱病变,分子生物学特点和遗传学表现相似,可通过LG-DCIS阶段进展为低级别浸润性导管癌(LG-IDC);ADH不是高级别导管内原位癌(HG-DCIS)的前驱病变,高级别浸润性导管癌(HG-IDC)具有不同的发生机制。细胞黏附分子表达异常,细胞外基质产生大量的基质蛋白酶使细胞间黏附性降低,降解基膜,促进ADH向IDC发展。

Breast atypical ductal hyperplasia （ADH） has the risk of progression into breast cancer, and there are characteristic molecular biological and genetic changes in ADH, which is to some extent similar to ductal carcinoma in situ （ DCIS）. The increase of cell proliferation index, hormone receptor expression and cell growth regulating factors may promote the formation of ADH. Chromosome abnormality and epigenetic changes may lead to the formation of ADH, among which 16p, 17q chromosome abnormality and promoter methylation of cancer related gene may be the early events of ADH. Studies have confirmed that ADH is the precursor of low grade ductal carcinoma in situ （LG-DCIS） which shares the similar molecular biological characteristics and genetic performance with ADH, and can progress to low grade invasive ductal carcinoma （LG-IDC） through LG-DCIS stage. Studies have also pointed out that ADH is not the precursor of high grade duetal carcinoma in situ （HG-DCIS）, and high grade invasive ductal carcinoma （HG-IDC） has different pathogenesis. With the abnormal expression of cell adhesion molecule, extracellular matrix produces a large number of matrix protease which resuhs in reduced cell-to-cell adhesion and degradation of basement membrane, and uhimately promotes the development of ADH to IDC.