Overlap of paraneoplastic granulocytosis and hypercalcemia

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Human neoplasm rarely accompanies with peripheral blood granulocytosis and humoral hypercalcemia. These paraneoplastic syndromes are essentially different entities. However, a few malignant neoplasms accompany both paraneoplastic syndromes. In this study, the mechanisms for overlap of the PB granulocytosis and hypercalcemia were examined by molecular biological analysis in the human tumor xenografts established in nude mice. We isolated 6 human malignant tumor xenografts which accompany with both PB granulocytosis and hypercalcemia in their host animals. All the 6 human xenografts co-express granulocyte-colony stimulating factor (G-CSF) and parathyroid hormone related protein (PTHrP) gene. Biologically active G-CSF protein secretion were confirmed in the sera of the host animals. And, the PTHrP transcripts revealed molecular heterogeneity in these tumor xenografts, suggesting of the alternative splicing mechanisms. One of the 6 xenograft (LC-GP-JCK) contain activated K-RAS oncogene (codon 12). The relationship between co-expression of G-CSF/PTHrP gene and RAS oncogene activation is interesting. Further analysis will be required.