Gland to Gland Heterogeneity in Histologically Normal Mucosa of Colon Cancer Patients Demonstrated by Monoclonal Antibodies to Tissue-specific Antigens1

Two of three monoclonal antibodies to tissue-specific antigens of isolated colonie glands revealed gland to gland heterogeneity of antigen expression in sections of the histologically normal colonie mucosa from patients with colorectal adenocarcinoma or various nonmalignant condi tions. A colon-specific goblet cell antigen (designated 3NM) was absent from rare, solitary glands randomly distributed among the otherwise strongly stained glands of distal colon. These 3NM-negative glands stained normally for the other two antigens studied and appeared mor phologically and histochemically normal. They occurred in 11 of 13 cancer patients and in each of the five patients with benign conditions with median incidences of 2.2 and 0.4 per 1000 glands, respectively. Gland heterogeneity was also demonstrated in both patient groups for a cell membrane antigen (designated 6NM). In cecum and ascending colon, glands staining strongly and weakly for 6NM were found intermixed. The weakly stained glands tended to predominate in cecum and first part of ascending colon, but they were completely replaced by strongly stained glands in more distal colon. The heterogeneity shown by both 3NM and 6NM appeared due to phenotypically distinct cell clones. Our observa tions indicate that histologically normal colonie mucosa contains antigenically diverse gland populations.