Immunolocalization of integrins in the normal and neoplastic colonic epithelium.

Abstract

Cryosections of normal colon (NC), tubular and villous adenomas (TA, VA), and variably differentiated colon adenocarcinomas (CA) were immunostained with monoclonal antibodies to alpha 1-6 and alpha v, and beta 1-4 integrin subunits; select samples were stained for cytokeratin (Ck) 20 and villin. In NC, alpha 2 staining was strongest in crypt cells; alpha 1,3 and alpha v, and beta 1,3 and beta 4, and Ck 20 and villin predominated in superficial enterocytes. In TA and VA, monolayered glands showed integrin, Ck 20 and villin patterns that differed slightly from both crypt and superficial enterocytes. Complex glands in VA showed decreased integrin staining and basal polarization; Ck 20 and villin were strong only in luminal cells. CA showed overall weaker integrin staining than adenomas. Regardless of invasion depth, well formed malignant glands mimicked TA; pleomorphic glands mimicked VA with focal basal integrin polarization and solid clusters displayed scanty integrins, uneven Ck 20, and villin in occasional cells. Diverse integrins in crypt compared with superficial enterocytes reflect changing adhesive requirements as cells migrate and terminally differentiate. Decreasing expression and altered distribution of integrins, Ck 20 and villin noted in TA, VA, and in CA of increasing grade indicate that certain adhesive and cytoskeletal features more closely relate to glandular architecture than to depth of invasion.