Distribution of tenascin, cellular fibronectins and integrins in the normal, hyperplastic and neoplastic breast.
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.
Koukoulis
G K
GK
Department of Pathology, Rush Medical College, Chicago, Illinois 60612-3864.
Howeedy
A A
AA
Korhonen
M
M
Virtanen
I
I
Gould
V E
VE
D001940:Breast / Q000033:anatomy & histology* / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology*; D015816:Cell Adhesion Molecules, Neuronal / Q000032:analysis*; D016326:Extracellular Matrix Proteins / Q000032:analysis*; D005260:Female; D005353:Fibronectins / Q000032:analysis*; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D016023:Integrins / Q000032:analysis*; D019063:Tenascin
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D016023:Integrins; D019063:Tenascin