Distribution of histocompatibility and leucocyte differentiation antigens in normal human colon and in benign and malignant colonic neoplasms

Abstract

Summary Monoclonal antibodies (McAbs) directed against the framework determinants of Class I and Class II products of the major histocompatibility complex (MHC) and against leucocyte differentiation antigens were used in an indirect immunoperoxidase technique to study their expression in normal, benign (adenomatous polyps) and malignant disease of the colon. Class I products (detected by the McAb 2AI) were strongly expressed on all cell types in normal and benign tissues but some carcinomas exhibited a heterogenous pattern of epithelial cell staining and 4/15 were completely negative. Class II products (detected by TDR3 1.1) were strongly expressed on cells (mainly B lymphocytes) within the lamina propria. In carcinomas TDR31.1 staining was mainly interstitial, but in 2/15, DR+ epithelial cells were also detected. In normal and benign tissues, leucocytes (reactive with 2D1) found predominantly in the lamina propria, comprised T cells mainly of the helper/inducer (OKT4) subset, DR+ cells in approx. equivalent proportion and a few OKM1+ cells mostly of macrophage morphology. Occasional intraepithelial lymphocytes were of cytotoxic/suppressor (OKT8) phenotype. In malignant neoplasms, there was wide inter and intra-tumour variation in the proportion of leucocytes which were heterogeneous with respect to cell type and confined mainly to the stroma. T cells were consistently predominant, but B cells and macrophages were also present. Two neoplasms showed unequivocal evidence of a shift (relative to peripheral blood) in favour of the OKT8+ subset, but in the majority of tumours OKT4+; and OKT8+ cells were present in roughly similar proportions. Natural killer cells (monitored with Leu7, HNK1) were virtually undetectable in both normal and malignant tissues. There were no apparent correlations between the extent and type of leucocyte infiltration, tumour differentiation or expression of MHC products. Some implications for the extrapolation of in vitro data on leucocyte function to the in vivo situation are discussed.

Expression of MHC products and leucocyte differentiation antigens in gynaecological neoplasms: An immunohistological analysis of the tumour cells and infiltrating leucocytes

“…In ovarian cancer, there is marked size variation and cytochemical heterogeneity among macrophages which is associated with a spectrum of activities from suppression to antibody-dependent cellular cytotoxicity (Haskill et al, 1982b). However, gynaecological cancers, like those of breast, colon and lung (Watanabe et al, 1983;Bhan & Des Marais, 1983;Whitwell et al, 1984;Csiba et al, 1984), contain few cells of natural killer phenotype.…”

“…Daar et al, 1984a). Depressed or heterogeneous expression of MHC Class I products, as detected by immunohistological procedures, is a property of some tumours of diverse histogenic derivation including breast (Fleming et al, 1981;Bhan & Des Marais, 1983;Rowe & Beverley, 1984;Whitwell et al, 1984) and to a lesser extent, colorectal carcinoma (Csiba et al, 1984). Other neoplasms, notably malignant melanoma (Ruiter et al, 1982) and certain histological categories of ovarian carcinoma (Kabawat et al, 1983) appear to express Class I antigens with greater consistency, a phenomenon which is apparently related to the predominantly T cell infiltrate which is a feature of these tumours.…”

“…With the exception of the B73.1 reagent, details of the McAbs used in this study have been given previously (Whitwell et al, 1984;Csiba et al, 1984) and are summarised in Table I Normal cervix MHC Class I antigens were strongly expressed on the lower one-third to one half of the squamous epithelium (Figure 3). In 10/14 samples endocervical glands were present, which were Class I positive.…”

“…Currently there is interest in whether this property is a requirement for the induction of autologous lymphoproliferative responses by tumour antigens of the MHC status of tumour cells and the in situ host response in a manner which has hitherto proved impossible using conventional histological techniques. In this study we extend this approach, previously applied in this laboratory to breast and colorectal carcinomas (Whitewell et al, 1984;Csiba et al, 1984) (Whitwell et al, 1984). Briefly, sections were incubated in the monoclonal antibody (McAb) (Whitwell et al, 1984).…”

Infiltration of mononuclear inflammatory cells into primary colorectal carcinomas: an immunohistological analysis

“…Eighty per cent of the lymphocytes expressed T cell characteristics, 17% B cell characteristics and 6% were null cells (Ebert et al, 1989). The ratio between helper/inducer cells (CD4+) and cytotoxic/suppressor cells (CD8+ in colorectal cancers has varied considerably in different studies (Csiba et al, 1984;Lennard et al, 1984;Allen and Hogg, 1985;Koch et al, 1985;Umpleby et al, 1985;Ebert et al, 1989).…”