Expression of the small cell carcinoma antigens of cluster-5 and cluster-5A in primary lung tumours

Abstract

Summary The expression of the small cell carcinoma (SCLC) antigens cluster-5 (antibody LAM8) and cluster-5A (antibody SWA20) was examined on a panel of routinely processed biopsy or surgical specimens of 290 lung tumours by immunoperoxidase staining. Antigen expression was largely restricted to SCLC. Of over 150 tissue samples evaluated, moderate or strong antigen expression was found in 49% (cluster-5) and 45% (cluster-5A). Concordance in expression of the two antigens was seen in 71% of SCLC samples, with 35% expressing both antigens strongly, 8% moderately and 28% being negative for both antigens. Antigen expression was independent of the morphological subtype of SCLC. (Stahel et al., 1985), antigens shared with white blood cells (Bunn et al., 1985;Cailland et al., 1984), neuroendocrine antigens (De Leij et al., 1985;Takahashi et al., 1986;Watanabe et al., 1987) and tumour-associated antigens (Waibel et al., 1987;Waibel et al., 1988). In the past, it has been very difficult to evaluate individual antibodies based on the original reports, since different laboratories varied widely on the material and methods used for the description of antibody and antigens. Since the First International Workshop for Small Cell Lung Cancer Antigens (Souhami et al., 1987), where antibodies have been analysed comparatively and five clusters of membrane antigens have been identified, the evaluation and reporting of individual antibodies has been greatly facilitated.We have previously reported on the characteristics of two antibodies, the IgM antibody LAM8 and the IgG2a antibody SWA20, which recognise closely related, but not identical membrane sialoglycoproteins heterogeneously expressed in SCLC (Stahel et al., 1986;Waibel et al., 1987Waibel et al., , 1988. By immunoperoxidase technique both antibodies stained equally well frozen and formalin fixed tissues of SCLC, while little or no reactivity was found with non-small cell carcinomas of lung, extrapulmonary carcinomas, and normal tissues, including bronchial epithelium and epithelium of the gastrointestinal tract, liver, kidney, pancreas, lymphoid organs, bone marrow, peripheral nerve and brain. Because of the virtual absence of expression in normal tissues, the antigens were called tumour-associated antigens of SCLC. In the First International Workshop on Small Cell Lung Cancer Antigens, the antibody LAM8 was designated to SCLC cluster-5 (CL-5) and the antibody SWA20 to SCLC cluster-5 associated (CL-5A) (Beverly et al., 1988).The aim of this study was to determine whether these two antibodies. could be used in formalin-fixed, paraffinembedded biopsy and surgical tissues obtained in a routine setting, and whether their restrictive reactivity with SCLC Correspondence: R.A. Stahel. Received 19 October 1988, and in revised form, 15 December 1988. could be confirmed when larger numbers of tissues of all types of primary lung tumours were examined. Materials and methods Tumour tissuesTumour tissues were obtained from files of the Institute of Pathology, Ruhr-University of Bochum,...

Cytotoxic activity of ricin A chain immunotoxins recognising cluster 1, w4 and 5A antigens associated with human small cell lung cancer

“…This antigen could be an appropriate target for the development of ricin A chain ITs with therapeutic potential designed to react with a high proportion of human SCLC tumours. The cluster 5A antigen recognised by SWA20 is a sialoglycoprotein that is highly selectively expressed by human SCLC and is present in about 50% of primary SCLC tumours Maier et al, 1989). Our studies indicate that ricin A chain ITs directed to this antigen could exert selective cytotoxic effects against the fraction of tumour cells that express the target antigen.…”

Monoclonal anti‐idiotypic antibody mimicking a tumor‐associated sialoglycoprotein antigen induces humoral immune response against human small‐cell lung carcinoma

“…SGP,-,,, is a membrane sialoglycoprotein with high selectivity of expression in small-cell carcinoma, and little or no expression in normal tissues (Stahel et al, 1986;Maier et al, 1989;Bernal et al, 1988). To facilitate investigations on the structural relationship between antigen and anti-idiotype and to have the high specificity of a uniform reagent, a monoclonal approach was chosen to obtain a P-type anti-idiotypic antibody which could substitute for the antigen.…”

Cytotoxic properties of a ricin A chain immunotoxin recognising the cluster-5A antigen associated with human small-cell lung cancer

“…Both cluster-5 and -5A antigens are strongly expressed on 45%-50% of SCLC tumours and co-ordinately expressed in about 35% [5]. Expression of these antigens is practically absent from other pulmonary and extrapulmonary tumours and occurs only at low levels in bronchial epithelium and other normal tissues [5,10].…”