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腱生蛋白、细胞纤连蛋白和整合素在正常、增生和肿瘤性乳腺中的分布

Distribution of tenascin, cellular fibronectins and integrins in the normal, hyperplastic and neoplastic breast.

作者信息

Koukoulis G K, Howeedy A A, Korhonen M, Virtanen I, Gould V E

机构信息

Department of Pathology, Rush Medical College, Chicago, Illinois 60612-3864.

出版信息

J Submicrosc Cytol Pathol. 1993 Apr;25(2):285-95.

PMID:7686813
Abstract

We present immunolocalization data on tenascin (Ten), and extradomains A and B (EDA-, EDB-) and oncofetal (Onc-) isoforms of cellular fibronectin (cFn), and alpha 1-6 and alpha v and beta 1-4 integrin subunits on cryosections of normal human breast, the spectrum of fibrocystic disease (FCD), and benign and malignant breast neoplasms. Fetal breast ducts were surrounded by broad Ten bands; adult breast ducts and acini were encompassed by thin continuous rims. In FCD, Ten was detectable and was clearly enhanced around hyperplastic ducts. Fibroadenomas showed uneven Ten periductal reactions while in all carcinomas, the stroma showed extensive and strong reactions that were most intense at the tumors' invasive edge. EDA-cFn's distribution was similar to Ten's but the staining was stronger while EDB- and Onc-cFn were virtually restricted to fetal breasts and carcinomas. In the normal adult breast, alpha 1,2,3 and alpha 6, and B1 and beta 4 integrins were detected in myoepithelial cells; weaker staining was also noted in the basolateral aspect of luminal cells; this profile was retained--and at times enhanced--in FCD, fibroadenomas and in situ carcinomas in which myoepithelial elements were present. In carcinomas, particularly in those of high grade, integrins tended to be reduced. However, mucinous carcinomas showed enhanced expression and the emergence of alpha 5 integrin that was not in the normal repertory; also a subset of infiltrating lobular carcinomas showed prominent alpha 1 and alpha 6 and beta 1 and--rarely--beta 4 staining distributed in delicate cytoplasmic processes (kinetopodia). These data indicate that the complex cell-matrix and cell-cell interactions of the normal breast are slightly altered in hyperplastic processes and benign neoplasms whereas profound chances occur in carcinomas. The latter display enhanced Ten and EDA- and Onc-cFn expression in particular, while most integrins appear decreased. Notably, mucinous and some lobular carcinomas display enhancement of certain integrins. The conspicuous localization of integrins in kinetopodia may be significant in relation to the invasive behavior of lobular carcinomas.

摘要

我们展示了关于腱生蛋白(Ten)、细胞纤连蛋白(cFn)的额外结构域A和B(EDA-、EDB-)以及癌胚(Onc-)亚型,以及α1-6、αv和β1-4整合素亚基在正常人类乳腺、纤维囊性疾病(FCD)谱以及良性和恶性乳腺肿瘤冰冻切片上的免疫定位数据。胎儿乳腺导管被宽阔的Ten条带包围;成年乳腺导管和腺泡被薄的连续边缘环绕。在FCD中,Ten可被检测到,并且在增生导管周围明显增强。纤维腺瘤显示出不均匀的Ten导管周围反应,而在所有癌中,间质显示出广泛而强烈的反应,在肿瘤的浸润边缘最为强烈。EDA-cFn的分布与Ten相似,但染色更强,而EDB-和Onc-cFn实际上仅限于胎儿乳腺和癌。在正常成年乳腺中,α1、2、3和α6以及β1和β4整合素在肌上皮细胞中被检测到;在管腔细胞的基底外侧也观察到较弱的染色;这种模式在FCD、纤维腺瘤和存在肌上皮成分的原位癌中得以保留,有时还会增强。在癌中,特别是高级别癌中,整合素往往减少。然而,黏液癌显示出表达增强以及正常情况下不存在的α5整合素的出现;此外,一部分浸润性小叶癌显示出突出的α1和α6以及β1,很少有β4染色分布在精细的细胞质突起(动纤毛)中。这些数据表明,正常乳腺复杂的细胞-基质和细胞-细胞相互作用在增生过程和良性肿瘤中略有改变,而在癌中则发生了深刻变化。后者尤其表现出Ten、EDA-和Onc-cFn表达增强,而大多数整合素似乎减少。值得注意的是,黏液癌和一些小叶癌显示出某些整合素的增强。整合素在动纤毛中的显著定位可能与小叶癌的侵袭行为有关。

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