Integrins and their accessory adhesion molecules in mammary carcinomas

Loss of polarization in poorly differentiated tumors

Massimo Pignatelli, Maria Rosaria Cardillo, Andrew Hanby, Gordon W H Stamp

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

The integrins are αβ heterodimeric transmembrane proteins mediating cell-substratum as well as cell-cell interactions. To identify the pattern of expression of the β1, β3, and β4 integrins and their accessory adhesion molecules in relation to the malignant phenotype of invasive breast cancer, we performed an immunohistochemical study for the α2β1 (VLA-2), α6β1 (VLA-6), αv and αvβ3 (vitronectin receptor), α6β4, carcinoembryonic antigen, and carcinoembryonic antigen-related molecules in a series of 37 invasive breast carcinomas. All integrin chains examined showed similar patterns in nonneoplastic breast tissue, with strong membrane staining of the myoepithelial cells and weak to moderate staining on the basolateral surfaces of the luminal cells. We found that downregulation of the α2 chain of VLA-2 occurs more frequently in poorly differentiated grade III invasive ductal carcinomas (IDCs) (P = .048). Loss of α6β4 seems also to occur more frequently in grade III IDC (seven of 11 cases, 63.6%) than in grade I II IDC (two of eight cases, 25%), although this did not reach statistical significance. Carcinoembryonic antigen and carcinoembryonic antigen-related antigens, which are known to function as accessory adhesion molecules, were found mainly in the cytoplasm of neoplastic cells and there was reduced membrane polarization in poorly organized tumors. In contrast the αvβ3, vitronectin receptor heterodimer recognized by the 23C6 monoclonal antibody was weak or absent in normal breast epithelium, and was weakly expressed in two of 19 (10%) IDCs and in nine of 18 (50%) invasive lobular carcinomas (P = .008). However, the αv chain detected with the antibody 13C2 was weakly to moderately expressed on nonneoplastic epithelium and at a similar intensity in 13 of 19 IDCs and 15 of 17 invasive lobular carcinomas, suggesting that in IDC the αv chain may be associated with a different β chain (possibly β1 or β5). No correlation between integrin expression and estrogen/progesterone receptor status was found. These data provide further evidence that in invasive breast carcinomas there is a widespread deregulated expression of integrins and their accessory adhesion molecules with loss of polarization. Changes in the expression and function of cell adhesion molecules, which control growth and differentiation, may have clinical relevance in the behavior of breast cancer.

Original languageEnglish
Pages (from-to)1159-1166
Number of pages8
JournalHuman Pathology
Volume23
Issue number10
DOIs
Publication statusPublished - 1992
Externally publishedYes

Fingerprint

Ductal Carcinoma
Integrins
Carcinoembryonic Antigen
Breast Neoplasms
Integrin alpha2beta1
Integrin alphaVbeta3
Lobular Carcinoma
Neoplasms
Breast
Epithelium
Staining and Labeling
Membranes
Cell Adhesion Molecules
Progesterone Receptors
Cell Communication
Estrogen Receptors
Cytoplasm
Down-Regulation
Monoclonal Antibodies
Phenotype

Keywords

  • breast carcinoma
  • carcinoembryonic antigen
  • integrins
  • very late antigens
  • vitronectin receptor

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Integrins and their accessory adhesion molecules in mammary carcinomas : Loss of polarization in poorly differentiated tumors. / Pignatelli, Massimo; Cardillo, Maria Rosaria; Hanby, Andrew; Stamp, Gordon W H.

In: Human Pathology, Vol. 23, No. 10, 1992, p. 1159-1166.

Research output: Contribution to journalArticle

Pignatelli, Massimo ; Cardillo, Maria Rosaria ; Hanby, Andrew ; Stamp, Gordon W H. / Integrins and their accessory adhesion molecules in mammary carcinomas : Loss of polarization in poorly differentiated tumors. In: Human Pathology. 1992 ; Vol. 23, No. 10. pp. 1159-1166.
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