Evaluation of CD43 expression in non-hematopoietic malignancies.

OBJECTIVES: CD43 is normally expressed only on the surface of leukocytes, and is considered a sensitive and specific marker for hematologic malignancies. As such, it may have diagnostic utility in confirming hematolymphoid lineage in cases that are negative for CD45. Aberrant CD43 expression has been described in non-hematopoietic tumors, although literature data on this topic is variable and sometimes contradictory. To clarify and expand on existing literature findings, we evaluated CD43 expression by immunohistochemistry (IHC) in a large cohort (307) of non-hematopoietic neoplasms, including poorly differentiated malignancies. METHODS: 17 tissue microarrays and sections from 19 individual cases were stained with CD43 (clone DF-T1) monoclonal antibody. The proportion of positive cells, stain localization (nuclear, cytoplasmic or membranous), and intensity (compared to internal leukocyte controls) were recorded in all cases. RESULTS: There were 98/307 (32%) positive cases, that showed focal weak nuclear staining in 1-25% of cells, including 23/25 (92%) pancreatic ductal adenocarcinomas; 31/34 (91%) breast invasive ductal carcinomas; 13/15 (87%) papillary thyroid carcinomas; 3/4 (75%) follicular thyroid carcinomas; 6/15 (40%) renal cell carcinomas; 9/28 (32%) lung adenocarcinomas; 1/13 (8%) lung squamous cell carcinomas (SCCs); 2/8 (25%) prostate adenocarcinomas; 8/62 (13%) colon adenocarcinomas; and 2/21 (10%) neuroendocrine neoplasms. None of the positive cases demonstrated strong, membranous CD43 expression comparable to that seen in background mature lymphocytes or segmented neutrophils. Negative cases included 11 cervical SCCs, 12 cervical adenocarcinomas, 19 urothelial carcinomas, 10 lung small cell carcinomas, 11 sarcomas, and 19 poorly differentiated carcinomas from various tissue sites. CONCLUSIONS: In our cohort, most non-hematopoietic neoplasms are negative for CD43 expression, with a subset showing focal, weak nuclear positivity. This data indicates that uniform and strong membranous staining appears to be specific to hematopoietic neoplasms.

IL-4 induces protection of vascular endothelial cells against killing by complement and melittin through lipid biosynthesis.

We have shown previously that cytokines IL-4 and IL-13 induce protection in porcine vascular endothelial cells (EC) against killing by the membrane attack complex (MAC) of human complement. This protection is intrinsic, not due to changes in complement regulatory proteins, and requires activation of Akt and sterol receptor element binding protein-1 (SREBP-1), which regulates fatty acid and phospholipid synthesis. Here we report that, compared to EC incubated in medium, IL-4-treated EC had a profound reduction in complement-mediated ATP loss and in killing assessed by vital dye uptake, but only a slight reduction in permeability disruption measured by calcein release. While controls exposed to complement lost mitochondrial membrane potential and subsequently died, protected EC maintained mitochondrial morphology and membrane potential, and remained alive. SREBP-1 and fatty acid synthase activation were required for protection and fatty acid and phospholipid synthesis, including cardiolipin, were increased after IL-4 stimulation, without increase in cholesterol content or cell proliferation. IL-4 also induced protection of EC from killing by the channel forming protein melittin, similar to protection observed for the MAC. We conclude that IL-4 induced activation of Akt/SREBP-1/lipid biosynthesis in EC, resulting in protection against MAC and melittin, in association with mitochondrial protection.

The effect of signal averaging on the reproducibility and reliability of measures of T-wave morphology.

Electrocardiographic repolarization abnormalities characterized by T-wave morphology parameters such as the principal component analysis ratio and the relative and the absolute T-wave residuum (TWR(rel) and TWR(abs)) are predictive of cardiovascular and/or all-cause mortality. However, when using a "10-second median beat" for analysis, the reported mean values for TWR(rel) vary widely and parameter reproducibility is somewhat suspect. In repeated electrocardiographic recordings conducted 1 month and 1 year apart on 15 and 27 healthy individuals, respectively, we studied the said T-wave morphology parameters in single complexes and in reduced noise signal averages containing 10 and 200 complexes. Considering all subjects, the mean (+/-SD) TWR(rel) was highest in a single complex (0.0345% +/- 0.0183%), intermediate in the 10-beat signal-averaged complexes (0.0125% +/- 0.0051%), and lowest in the 200-beat signal-averaged complexes (0.0078% +/- 0.0036%) (P < .0001), with the same trend also observed in the TWR(abs) but not in the principal component analysis ratio. Reproducibility as quantified by within-subject variance and reliability as quantified by the intraclass (intrasubject) correlation coefficient also improved as the number of T-wave complexes analyzed increased. We conclude that signal averages consisting of more than 10 complexes (or more than 10 seconds worth of complexes) are required to produce reproducible and reliable values for TWR(rel) and TWR(abs).