No abstract

Most of the hereditary breast cancers are attributed to constitutive alterations of either BRCA1 or BRCA2 genes; nonetheless, germline mutations of these genes iǹ high risk' families are found less frequently than expected from linkage data. Recent ®ndings suggest that major genomic rearrangements of the BRCA1 gene might account for at least some of the apparently mutation negative cases. We studied 60 aected probands belonging to families with a strong history of breast and/or ovarian cancer who scored negative for BRCA1 gene mutations by PTT and SSCP analysis. DNA was analysed by the Southern blotting procedure using three dierent restriction enzymes, and two probes obtained by RT ± PCR of the 5' and 3' BRCA1 coding sequence. A 3 kb deletion encompassing exon 17 and causing a frameshift mutation was identi®ed in two independently ascertained families. RT ± PCR and longrange DNA PCR were employed to characterize the rearrangement that was ®nally shown to be the result of a recombination between two very similar Alu repeats. This type of mutation is not identi®ed by the conventional methods of mutation detection which are based on PCR ampli®cation of single exons. Therefore, further search for gene rearrangements is needed to better de®ne the proportion of`high risk' families that might be explained by gross genomic alterations of the BRCA1 gene.

The diagnostic accuracy of an indirect immunofluorescence antibody test (IFAT) for Strongyloides stercoralis at different serum antibody titers was evaluated. To assess diagnostic sensitivity, sera from 156 patients with known strongyloidiasis were collected. Negative control sera were obtained from a composite group of 427 subjects (blood donors and hospitalized patients). With an area under the receiver-operating characteristic plot of 0.98, the IFAT showed a high level of diagnostic accuracy for strongyloidiasis. An antibody titer of >1:20, with 97% sensitivity and 98% specificity, was identified as the diagnostic threshold with the best overall performance. Cross-reactions were evaluated with 41 additional samples from patients with other known helminth infections, and the IFAT detected low-titer positivity in only one subject with filariasis. A positive IFAT result at an antibody dilution of >1:80 was virtually 100% specific, with 71% sensitivity. To test the usefulness of the IFAT as a monitoring tool, the changes in specific-antibody titers after treatment in a group of 155 patients were evaluated. Seroreversion or a decrease in antibody titer of twofold or more was observed in 60% of the patients. Response to treatment was directly correlated to the initial antibody titer, and a baseline titer of >1:80 was identified as the best predictor of response. In conclusion, a positive IFAT result at an antibody dilution of >1:20 is the optimal cutoff for screening. A titer of >1:80, with virtually no false-positive result, is a reliable cutoff for a serological assessment of treatment efficacy and for inclusion in clinical trials.

A primary cutaneous form of peripheral T-cell lymphoma (PTCL) and a low grade B-cell non-Hodgkin's lymphoma that was classified as a variant of hairy cell leukemia (HCL) were simultaneously diagnosed in a 79-year-old woman by both phenotypic and genotypic analyses. The coexistence of a T- and B-cell lymphoma in the same patient is rare, and, to our knowledge, this particular association has not been previously described. The patient was referred to our Department for evaluation of multiple cutaneous itchy, reddish plaques; laboratory analyses disclosed a lymphocytosis, that presented 6 years earlier. A bone marrow aspirate showed a 50% B-cell interstitial infiltrate, while a skin biopsy surprisingly revealed a PTCL. Clonality of both neoplastic processes was assessed by Southern blot analysis. The indolent clinical course of the cutaneous disease, and the low and stable number of circulating neoplastic T cells supported the diagnosis of a mycosis fungoides (MF)-like PTCL. Possible oncogenic events and/or putative underlying viral infections which could have played a role in the occurrence of B- and T-cell non-Hodgkin's lymphomas in the same patient are discussed.

In the present study we show that two-dimensional (2-D) maps together with immuno-detection allow the precise identification of important leukocyte differentiation and tumor markers (e.g., CD3 and CD5), and important cell cycle regulatory molecules such as cyclin dependent kinases, notably CDK6. In addition, the comparative evaluation of molecular expression (e.g., CD5) in maps developed with normal and lymphoma samples can provide reproducible and precise information regarding the molecular expression in different cell populations. Accordingly, we could detect a much increased level of expression of CD5 in mantle cell lymphoma, up to ten times higher than in the control. In addition, CD5 in tumor tissues seems to be microheterogeneous as compared to normal samples.