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Mutations in the APC gene give rise to familial adenomatous polyposis (FAP) and also occur in many, perhaps most, sporadic colon cancers. By screening with single-strand conformation polymorphism analysis we identified several mutations in a small region of the APC gene in both FAP and sporadic cancers. These mutations were either point mutations or small deletions or insertions causing frameshifts, and all generated stop codons. One 5 base-pair deletion was found in a sporadic colon tumour, a colorectal cancer cell line derived from a sporadic colon tumour, and in four unrelated FAP patients. This mutation produces distinctive heteroduplex bands, which can be detected with a simple non-radioactive assay. Our findings suggest that highly localised short sequences, essentially runs that code for adenine and thymine, may account for up to 20% of all observed APC mutations.

Two tumour-associated monoclonal antibodies, HMFG1 and HMFG2, were labelled with iodine-123 and used to detect primary and metastatic ovarian, breast, and gastrointestinal neoplasms by external body scintigraphy in twenty patients with advanced disease. Tumours became visible 3 min to 18 h after injection of labelled antibody. The presence of antibody in the tumours was confirmed by autoradiography and immunoperoxidase staining of surgically removed tissues. The mean tumour uptake of radiolabel was 0.6% of the injected amount. These antibodies can therefore localise specifically to tumours and successful imaging can thus be achieved. This method can complement existing diagnostic techniques and also provide a basis for a selective therapeutic approach to malignant disease.

Two monoclonal antibodies, HMFG2 and AUA1, raised against epithelial-cell determinants were used to detect carcinoma cells in smears of serous effusions. Both antibodies react strongly with malignant epithelial cells but not with normal mesothelial or endothelial cells. A third antibody, 11-4.1, which does not react with any human tissue, was used as a negative control. An immunoperoxidase-staining technique was applied to smears of cells from serous effusions. The immunohistochemical diagnosis was in agreement with the cytological diagnosis. In cases with equivocal cytology in which the diagnosis became clear in later samples, the immunohistochemical diagnosis gave the correct result. With this combination of tumour-associated monoclonal antibodies a confident diagnosis of malignancy in serous effusions can be made.

When the HLA types of 80 pre-eclamptic women and their husbands and 83 control couples were compared significantly more pre-eclamptic women had only one identifiable HLA B antigen, and were presumed to be homozygous at this locus. Those who were homozygous for HLA B were more likely to be homozygous for HLA A as well, and more likely to be homozygous for HLA A as well, and to have more severe pre-eclampsia. There was neither increased HLA incompatibility nor greater antigen-sharing between pre-eclamptic women and their husbands, but maternal HLA A and B homozygosity reduced the number of antigenic disparities between pre-eclamptic women and their husbands. The data are consistent with the hypothesis that maternal recessive immune-response genes may contribute to the development of pre-eclampsia. Alternatively maternal HLA homozygosity may predispose to fetal changes comparable to runting.

A monoclonal antibody (H17E2) against placental alkaline phosphatase (PLAP) and testicular placental-like alkaline phosphatase was labelled with indium-111 and used in radioimmunoscintigraphy of 15 patients known or suspected to have germ-cell carcinoma of the testis or carcinoma of the ovary or cervix. Good images of neoplastic lesions were obtained in most patients with active disease. In 1 patient with testicular teratoma and elevated human chorionic gonadotropin who had a normal computed tomography scan, the labelled antibody located microscopic disease in a lymph node, which was then removed. No false positive localisation was seen in patients with PLAP-negative tumours or sites of inflammation. This method may be helpful in the diagnosis, staging, and monitoring of PLAP-positive neoplasms of testicular, ovarian, and cervical origin.