Prognostic significance of antigenic heterogeneity, Gleason grade, and ploidy of lymph node metastases in patients with prostate cancer.

We retrospectively evaluated 51 prostate cancer patients found to have pelvic lymph node metastases at the time of pelvic lymphadenectomy and 125I implantation. All of them were followed until death or for a minimum of 70 months. Rabbit polyclonal anti-PSA, anti-PAP, anti-PSP-94, and mouse TURP-27 monoclonal antibodies were used in immunohistochemical evaluation of the metastatic lesions. In addition, Gleason grade and ploidy were assessed and correlated. No tumor with a Gleason grade of less than 7 could be found in the metastatic lymph nodes. Time to progression (P = .003), disease-specific survival (P = .009), and overall survival (P = .003) were significantly shorter in patients whose tumors had a primary Gleason pattern of 5 (grade 9 or 10). In the PSA study, patients whose tumors were reactive in more than 75% of cancer cells experienced significantly longer survival than those with less than 75% of cancer cells expressing PSA (P = .0006 log rank test). The means of overall survival +/- SEM were 71.5 +/- 5.0 and 34.9 +/- 5.4 months, respectively. Similar correlations were found with disease-specific survival and time to progression. Patterns of PAP expression and TURP-27 reactivity were not prognostically useful, whereas PSP-94 expression may add some additional information. These data suggest that evaluation of tissue PSA heterogeneity in lymph node metastases may offer additional prognostic information on prostate cancer patients. Better prediction of individual prognosis may be possible with the combined use of Gleason grade, flow cytometry, and PSA expression.     

Cellular and molecular characterization of the role of the flk-2/flt-3 receptor tyrosine kinase in hematopoietic stem cells

The flk-2/flt-3 receptor tyrosine kinase was cloned from a hematopoietic stem cell population and is considered to play a potential role in the developmental fate of the stem cell. Using antibodies derived against the extracellular domain of the receptor, we show that stem cells from both murine fetal liver and bone marrow can express flk-2/flt-3. However, in both these tissues, there are stem cell populations that do not express the receptor. Cell cycle analysis shows that stem cells that do not express the receptor have a greater percentage of the population in G0 when compared with the flk-2/flt-3- positive population. Development of agonist antibodies to the receptor shows a proliferative role for the receptor in stem cell populations. Stimulation with an agonist antibody gives rise to an expansion of both myeloid and lymphoid cells and this effect is enhanced by the addition of kit ligand. These studies serve to further illustrate the importance of the flk-2/flt-3 receptor in the regulation of the hematopoietic stem cell.     

Management of malignancy-associated hypercalcemia

Rehydration and bisphosphonates represent the mainstay of the management of hypercalcemia associated with malignancy with successful achievement of normocalcemia in some 90% of patients. New experimental approaches are currently being tested. and the antiosteoclastic potential of osteoprotegrin appars to be promising.     

The effectiveness of radiation therapy in the treatment of bone metastases from breast cancer

The authors studied 75 patients with 158 areas of bone metastases from breast cancer treated by radiation therapy. The treatment regimen used was usually 2000 to 2500 rads delivered over a period of 2 weeks. Both subjective and objective responses were evaluated. This dose schedule proved to be highly effective in symptomatic relief and in healing osteolytic lesions; various levels of pain relief for about one year were observed in 96% (151/158 treatment areas), and radiographic evidence of recalcification was observed in 78% (73/94 treatment areas examined by serial radiography). After cases from previous studies were incorporated, the subjective response rate of the overall group was 91% (191/212) for a mean duration of 12 months, and the objective response rate was 75% (151/202) for a mean duration of 9 months.