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Protein kinase C-beta II (PKC-beta II) expression has been reported to indicate inferior prognosis in diffuse large B-cell lymphoma (DLBCL) treated with anthracycline-based chemotherapy. This study compared prognostic significance of immunohistochemically determined PKC-beta II expression in de novo DLBCL treated with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) chemotherapy with and without rituximab. Outcomes were assessed in 80 consecutive patients, 48 treated with CHOP, and 32 with rituximab plus CHOP (R-CHOP). PKC-beta II expression correlated with inferior overall survival (OS) and progression-free survival (PFS) in CHOP-treated patients with low-risk International Prognostic Index (IPI) disease (0-2 adverse factors), but not in the overall patient group unstratified by IPI. PKC-beta II expression correlated with inferior OS and PFS in R-CHOP-treated patients unstratified by IPI status. Immunohistochemically demonstrated PKC-beta II expression thus identified patient subgroups where alternative treatment strategies may confer superior outcome. We now report that PKC-beta II expression has prognostic significance not only for CHOP therapy in low-risk IPI disease, but also for all patients receiving CHOP plus rituximab.

Hypercalcemia is an important complication in multiple myeloma as well as T-cell leukemia/lymphoma, and is moderately common in high and intermediate grade non-Hodgkin's lymphoma. The underlying mechanism has been unclear because the neoplastic cells are usually present in the bone marrow, where they are in a position to produce short range effects on bone resorption which are difficult to identify. This contrasts with the situation in hypercalcemia associated with non-metastatic carcinoma, where it has been clearly demonstrated that the most common cause is release from the tumor of a humoral mediator, Parathyroid Hormone-related Protein (PTHrP). Roles have been advocated in multiple myeloma for release of a number of other cytokines with osteolytic capacity on the basis of their enhancement of osteolytic activity in cultured fetal rat bone, although a causal relationship in patients has not been established. PTHrP has more recently been implicated in the genesis of hypercalcemia in patients with hematological malignancies by the demonstration in a proportion of cases of increased circulating levels of PTHrP, comparable to those in hypercalcemia due to cancer. Immunohistochemical studies indicate neoplastic hemopoietic cells can contain PTHrP, and thus have the capacity to act in a paracrine manner to enhance local bone resorption and contribute to the development of hypercalcemia.

surrounding the excised cancer exceeded that in the normal thyroid tissue of four other patients with thyroid cancer who had no known exposure to arsenic, and was considered to refl ect retention of arsenic for 10 years after completion of ATO administration that could have promoted the development of thyroid cancer. Th ere are a number of questions as to the extent to which these observations provide evidence of an unequivocal link between tissue retention of arsenic after ATO therapy and an increase in cancer risk. Th e arsenic concentration in thyroid tissue of the unexposed control subjects was highly variable, ranging from virtually negligible to approximately half that in the ATO trioxide treated patient, which in such a limited number of patients prevented statistically signifi cant confi rmation of a diff erence between arsenic concentrations in thyroid tissue of the patient and the subjects who had not