C-erbB-2 expression and its relationship with ploidy, p53 abnormalities and epidermal growth factor receptor content in human non-small cell lung cancer.

This study attempts to clarify the role of c-erbB-2 overexpression in human non-small cell lung cancer (NSCLC) and relate it with the p53 alterations, DNA index (D.I.) and epidermal growth factor receptor (EGFR) content in sixty four patients with NSCLC. c-erbB-2 and EGFR quantification were carried out from tissue homogenates using quantitative ELISA procedures. p53 alterations were determined by immunohistochemical (IHC) detection with the monoclonal antibody DO-7 and analysis for p53 mutations on exons 4 to 8 by single strand conformation polymorphism (SSCP). The D.I. was performed by flow cytometry. c-erbB-2 hyperexpression was found in 13 of 58 LC (22%), and it was closely associated with hyperdiploid tumors (D.I. >1.3; P = 0.00). The p53 abnormalities detected by SSCP were statistically more frequent in hyperdiploid tumors (16/25; P = 0.015) than in diploid ones (8/30). No relationship between the results of IHC p53 and SSCP was found. The patients with c-erbB-2 hyperexpressing tumors were prone to have frequent relapses (P = 0.03), although the patients with hyperdiploid NSCLC are the ones with the highest relapse rate (P = 0.008). From the results obtained in this study the following conclusions can be drawn: (a) c-erbB-2 hyperexpressing NSCLC are associated with abnormalities in other biological markers and with a greater rate of relapses; (b) SSCP seemed to be more specific that IHC to detect p53 molecular abnormalities; and (c) the D.I. is the parameter more tightly related with relapse.

Relationship of p53 molecular abnormalities with flow cytometry and growth factor receptor content in lung cancer.

This study attempts of clarify the oncological significance of the p53 molecular abnormalities and p53 expression in lung cancer (LC) and their relationship with flow cytometry (FC) parameters and epidermal growth factor receptor (EGFR). The study includes 65 samples taken from both LC and normal lung (NL). The p53 molecular abnormalities of exons 4-8 were studied by single strand conformation polymorphisms (SSCP) and the loss of heterozygosity (LOH) of exon 4 by the Metzler method. P53 protein was detected by Western blot. EGFR was determined by a radioligand assay using [125I]EGF. The FC parameters S phase fraction (SPF), DNA index (D.I.), G1G0 and growth rate (G2M + SPF) were evaluated from cellular monosuspensions. The LC with SSCP p53 molecular abnormalities have a significantly higher EGFR content (P < 0.001), SPF (P < 0.007), D.I. (P < 0.017) and a lower proportion of G1G0 cells (P < 0.04) than LC with no molecular abnormalities. No relationship between p53 molecular abnormalities and tumor TN or evolutive events was found. Neither the relationship between the molecular results and p53 expression detected by Western blot nor that of the p53 expression detected by Western with FC parameters or EGFR could be shown. In NL the growth fraction cells decrease significantly (P < 0.05) with the intensity of p53 expression. The lack of biological functionality of p53 with molecular abnormalities seemed to relate to fast growing LC whereas p53 expression detected by Western seemed more related to the wild type of p53.

[Thrombopenic purpura associated with human immunodeficiency virus infection. Analysis of 24 cases]. / Púrpura trombopénica asociada a infección por virus de la inmunodeficiencia humana. Análisis de 24 casos.

In 24 cases of thrombopenic purpura associated with human immunodeficiency virus infection the clinical, immunological and therapeutic features were evaluated. Thrombopenia resulted in clinical manifestations in 20 patients. Splenomegaly was found in only one fourth of patients. Antiplatelet antibodies were found in 9 patients, and thrombopenia was associated with anemia in 37% of cases and with leukopenia in 21%. Bone marrow examination showed megakaryocyte hyperplasia in two thirds of the patients. The major immunological abnormalities were an inverted helper/suppressor T lymphocytes ratio, a reduction in the number of helper T lymphocytes, polyclonal hypergammaglobulinemia, and increased serum concentrations of circulating immunocomplexes. The different therapeutic modalities, steroids, vincristine, danatrol and plasma exchange, resulted in short responses; only two patients had normal platelet counts. The median follow-up was 14 months; during this time three patients fulfilled the criteria of acquired immunodeficiency syndrome.