[Retrospectively detectable carcinomas: review of the literature]. / Cancers rétrospectivement visibles: revue de la littérature.

Retrospectively visible cancers are defined as interval cancers or screen-detected cancers (missed cancers) which are judged visible on prior screening mammogram. There are two kinds of retrospectively visible cancers: "actionable" cancers and nonspecific findings that do not warrant recall in normal practice. Nonspecific findings are twice more frequent than actionable cancers. The rate of missed breast cancers in screening is estimated at 25% (13-41%). Missed breast cancers are masses or calcifications. Masses are twice more frequent than calcifications. Missed breast cancers result from detection errors (location in retroglandular region or at the edge of glandular tissue, architectural distorsion) and interpretation errors (findings judged as benign). Detection errors could be limited by double reading and CAD, interpretation errors by better knowledge of BIRADS classification which needs specific training.

Immunoradiometric assay of succinylated corticotropin: an improved method for quantification of ACTH.

In this paper we describe the development and the evaluation of a new type of immunoassay for human corticotropin (ACTH). We succeeded, by using an original approach based upon immunization with ACTH derivatized with succinic anhydride, in raising monoclonal antibodies against this poorly immunogenic peptide. Three of the antibodies were selected to develop an immunoassay for ACTH. The assay requires the prior succinylation of the plasma samples for optimal sensitivity and specificity. This acylation treatment is fast, reproducible, and, in addition, improves the stability of the ACTH molecule in plasma, thus facilitating sample handling. The assay is performed in only 3 h with a detection limit of 0.7 ng/L. Analytical evaluation showed excellent specificity, reproducibility, and reliability. A comparison with two commonly used but time-consuming ACTH IRMAs was carried out by assaying several plasma samples in parallel and gave in both cases very good correlation.

A novel method for the production of antibodies against ACTH: their characterization and use in epitope mapping.

Our earlier attempts at immunization with human adrenocorticotropin hormone (ACTH) were unsuccessful and we therefore developed a new strategy including the chemical modification of the hormone by succinic anhydride in order to increase its immunogenicity. This process allowed us to obtain antisera with titers of up to 1/1000 and yielded 39 anti-succinylated ACTH (sACTH)-secreting hybridomas. Subsequently, the epitopes of sACTH were mapped by testing monoclonal antibodies two by two for simultaneous binding to sACTH and for their capacity to recognize its succinylated fragments 1-13, 1-17 and 1-24. The results, obtained with the use of radioactive tracers, were confirmed by and complemented with experiments conducted with biosensor technology. Seven groups of antibodies were defined on the basis of their pattern of reactivity and it was shown that four monoclonal antibodies could bind simultaneously to sACTH. Their dissociation constants (Kd) for sACTH were calculated and ranged from 10(-8) M to 10(-11) M. In order to obtain a fast and sensitive immunoassay for the hormone, we developed a protocol for the chemical modification of ACTH in serum and the most efficient monoclonal antibodies were selected on the basis of the epitope map and of their dissociation constants.

A novel protein immunoassay with predetermined specificity using monoclonal antibodies against tryptic fragments: application to HIV P24 antigen.

We have developed a new protein immunoassay method which uses antibodies raised against synthetic peptides. These synthetic peptides are selected to correspond to fragments of the protein that can be obtained by proteolytic treatment of the protein by trypsin. Just before assay, biological samples are treated with trypsin to liberate the fragments which bind to the anti-peptide antibodies with high affinity. The exact specificity of the assay is predetermined by the amino acid sequence of the fragment which may be either conserved within a family of antigens or, conversely, entirely specific for a particular protein. This method has been successfully employed in the development of an immunoassay for HIV P24 antigen. In that case, peptides were selected that were strongly conserved among the different HIV-1 and HIV-2 strains. This methodology has permitted the development of a sensitive immunoassay with a broad specificity despite many amino acid variations between HIV strains. The methodology could be extended to other protein antigens.