Diagnostic performance of the CellaVision preclassification neutrophil count - time to bypass the reclassification?

OBJECTIVES: The objective of this study was to perform a method comparison between the CellaVision preclassification neutrophil count and the reclassification neutrophil count performed by trained laboratory technicians, and to evaluate the diagnostic performance of the preclassification neutrophil count at clinical decision levels. METHODS: We retrospectively identified patient samples through 2019-2022 in which the differential count was performed on Cellavision (n = 4,354). Data on sample characteristics and leukocyte- and differential counts was extracted from the electronic medical journal. For each sample, data containing the pre- and reclassification leukocyte classification, respectively, was extracted from the Cellavision software. Method comparison between the pre-and reclassification neutrophil count was performed using Bland Altman analysis. Diagnostic performance of the preclassification neutrophil count was evaluated according to four pre-specified categories of results with the reclassification as reference method. RESULTS: The median difference between the pre- and reclassification neutrophil count was 0.044 x 109/L. The preclassification neutrophil count categorised 95.6% of all samples correctly according to the four categories. The sensitivity, specificity, positive predictive value and negative predictive value for detecting neutrophilia > 7.00 x 109/L was 98.8%, 97.2%, 95.8%, and 99.2%, respectively. In samples with leukopenia (n = 543), the sensitivity, specificity, positive predictive value and negative predictive value for detecting severe neutropenia (< 0.50 x 109/L) was 97.7%, 99.1%, 98.6%, and 98.5%, respectively. CONCLUSION: The diagnostic performance of the CellaVision preclassification neutrophil count was satisfactory. The preclassification neutrophil count may be released to the electronic medical journal to improve turnaround time and benefit laboratory management.

Epigenetic Silencing of LRP2 Is Associated with Dedifferentiation and Poor Survival in Multiple Solid Tumor Types.

More than 80% of human cancers originate in epithelial tissues. Loss of epithelial cell characteristics are hallmarks of tumor development. Receptor-mediated endocytosis is a key function of absorptive epithelial cells with importance for cellular and organismal homeostasis. LRP2 (megalin) is the largest known endocytic membrane receptor and is essential for endocytosis of various ligands in specialized epithelia, including the proximal tubules of the kidney, the thyroid gland, and breast glandular epithelium. However, the role and regulation of LRP2 in cancers that arise from these tissues has not been delineated. Here, we examined the expression of LRP2 across 33 cancer types in The Cancer Genome Atlas. As expected, the highest levels of LRP2 were found in cancer types that arise from LRP2-expressing absorptive epithelial cells. However, in a subset of tumors from these cancer types, we observed epigenetic silencing of LRP2. LRP2 expression showed a strong inverse correlation to methylation of a specific CpG site (cg02361027) in the first intron of the LRP2 gene. Interestingly, low expression of LRP2 was associated with poor patient outcome in clear cell renal cell carcinoma, papillary renal cell carcinoma, mesothelioma, papillary thyroid carcinoma, and invasive breast carcinoma. Furthermore, loss of LRP2 expression was associated with dedifferentiated histological and molecular subtypes of these cancers. These observations now motivate further studies on the functional role of LRP2 in tumors of epithelial origin and the potential use of LRP2 as a cancer biomarker.