The spectrum of morphomolecular abnormalities of the E-cadherin/catenin complex in pleomorphic lobular carcinoma of the breast.
Pleomorphic lobular carcinoma of the breast is a high nuclear grade variant of lobular carcinoma. E-cadherin, a tumor-invasion suppressor gene, codes for a transmembrane protein that functions in intercellular adhesion. The E-cadherin protein internal domain binds with alpha, beta, gamma, and p120 catenins to anchor the E-cadherin complex to the actin cytoskeleton of the cell. The E-cadherin gene is routinely mutated in lobular neoplasia. This study examines the morphomolecular spectrum of the components of the E-cadherin-catenin complex in lobular neoplasia. Fifteen cases of pleomorphic lobular neoplasia, 8 cases of classic lobular neoplasia and 4 ductal carcinomas were studied. Normal breast epithelium and invasive ductal carcinomas all showed intense linear cell membrane immunostaining with antibodies to E-cadherin, alpha, beta, gamma, and P120 catenins. Membrane immunostaining of the catenin antibodies in lobular neoplasia was negative, except for rare cases that displayed beaded or dotlike patterns. Cytoplasmic immunostaining patterns for all lobular lesions included coarse paranuclear granules of beta catenin or diffuse intense cytoplasmic staining for P120 catenin. These immunostaining patterns demonstrate that catenins alpha, beta, gamma, and p120 are routinely dislocated from the cell membrane into the cytoplasm in lobular neoplasia and that the disrupted catenin patterns parallel absence of membrane E-cadherin in all cases. The diffuse cytoplasmic immunostaining of p120 in lobular neoplasia may be useful diagnostically as a positive marker for lobular neoplasia.
Dabbs
David J
DJ
Department of Pathology, Magee-Women's Hospital of University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. ddabbs@upmc.edu
Kaplai
Malathy
M
Chivukula
Mamatha
M
Kanbour
Anisa
A
Kanbour-Shakir
Amal
A
Carter
Gloria J
GJ
D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000473:pathology*; D015820:Cadherins / Q000032:analysis*; D018275:Carcinoma, Lobular / Q000175:diagnosis / Q000473:pathology*; D051177:Catenins / Q000032:analysis*; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness; D011379:Prognosis
D015820:Cadherins; D051177:Catenins