Accurate prognostic parameters in prostate biopsies are needed to better counsel individual patients with prostate cancer. We evaluated the prognostic impact of morphologic and immunohistochemical parameters in preoperative prostate cancer biopsies. A consecutive series of prostate biopsies of 279 men (72% with clinical stage T1c and 23% with T2) who subsequently underwent radical prostatectomy was prospectively analysed for Gleason score, number and percentage of positive cores (NPC, PPC), total percentage of biopsy tissue with tumour (TPT), maximum tumour percentage per core (MTP), and expression of Ki67, Bcl‐2 and p53. All biopsy features were significantly associated with at least one feature of the radical prostatectomy specimen. pT stage was independently predicted by PSA, seminal vesicle invasion by Ki67 LI, positive margins by PSA and MTP, large tumour diameter by PSA and PPC, and Gleason score by biopsy Gleason score, MTP, and Ki67 LI, respectively. Biopsy Gleason score, NPC (1 vs. >1), TPT (<7 vs. ≥7%), and Ki67 LI (<10 vs. ≥10%) were significant predictors of biochemical recurrence after radical prostatectomy (p < 0.01, each). KI67 LI was the only independent prognostic factor in case of a low TPT (<7%) or low Gleason score (<7), the hazard ratio being 6.76 and 6.44, respectively. In summary, preoperative Gleason score, NPC, TPT and Ki67 LI significantly predict the risk of recurrence after radical prostatectomy, and Ki67 is an independent prognosticator in biopsies with low‐volume or low‐grade prostate cancer. Analysis of Ki67 LI in these biopsies may help to better identify patients with clinically insignificant prostate cancer. © 2008 Wiley‐Liss, Inc.

Objective. The arthritogenic potential of the cationic outer surface proteins (Osp) from Borrelia burgdorferi was tested in rats.Methods. Water-soluble Osps were prepared by butanol extraction and were administered by intraarticular injection. Tissue injury was assessed by scintigraphy and histology.Results. A mild arthritis was seen in naive rats. Preimmunized animals had more severe, longer lasting bouts of inflammation.Conclusion. The Osps of Borreliu burgdorfen are potent arthritogens in rats. These immunodominant antigens may play a role in the development of Lyme arthritis in humans.Arthritis is a frequent complication of Borreliu burgdorferi infection. Up to 60% of patients with untreated erythema chronicum migrans develop Lyme arthritis. About half of these patients experience intermittent attacks of inflammation and 10% develop chronic arthritis (1). In one study, bacteria were demonstrated in discrete foci within the structures of arthritic joints (2), and successful cultivation of Borreliu from synovial fluid has also been reported in a limited number of cases (3-5). Nevertheless, whether the induction and maintainance of Lyme arthritis requires the presence of bacteria or their products within the affected joints remains an unanswered question. There are approaches for establishing animal models of Lyme arthritis using live organisms. In rats and mice, the severity of arthritis following infection was found to be age dependent; young animals developed more severe inflammation (6,7). Arthritis has also been induced by injecting B burgdorferi into the joints of irradiated hamsters (8). In immunodeficient SCID mice, Borreliu infection leads to persistent spirochetemia, accompanied by multiple organ manifestations, including chronic joint inflammation (9). These models have increased our understanding of the biology of Lyme disease. It appears that arthritis develops best when the host animal's immune system is either immature or blatantly compromised. The underlying immunopathogenic mechanisms leading to Lyme arthritis in the presence of an intact immune system have not yet been clarified.Previous studies of rodents have shown that cationic antigens, including bacterial products, can be potent inducers of allergic arthritis (10-13); anionic antigens are not effective in this experimental setting (for review, see ref. 13). Postulating that the inflammatory process characteristic of Lyme arthritis may be an antigen-driven event, we sought putative cationic arthritogens from B burgdorferi. The most abundant cationic molecules possessed by B burgdorferi are the outer surface proteins (Osps) (14,15), which are also the immunodominant antigens in chronic borrelial infection (15,16). We were able to show that the Osps, in complexed form, are capable of inducing severe joint disease in healthy adult rats. MATERIALS AND METHODSAntigens. The Osp complex was prepared from B burgdorferi in aqueous form, as described previously (17). Briefly, late log cultures of B burgdorferi strains GeHo (a Freiburg area skin isol...

The anti-tumor activity of partially purified tumor necrosis factor (TNF) was analysed in combination with chemotherapeutic drugs against intradermally transplanted Meth A sarcoma. Tumors were allowed to grow until they reached an average diameter of about 8 mm. TNF was given once i.v. (16,000 units as determined on L-M cells) and the chemotherapeutic agents adriamycin (1-10 mg/kg), 5-FU (3-100 mg/kg), cyclophosphamide (50-200 mg/kg) were applied once i.p. 4 hr after TNF injection. The strongest anti-tumor effects in normal BALB/c mice were observed when TNF was combined with the following doses of chemotherapeutic agents: cyclophosphamide 100 mg/kg, adriamycin 5 mg/kg, 5-FU 30-100 mg/kg. The most effective combinations induced complete regressions. When TNF was combined with varying doses of adriamycin and cyclophosphamide, bell-shaped dose-response curves were obtained. Experiments were repeated in Meth A sarcoma-bearing BALB/c nu/nu mice. In this case TNF combinations with cyclophosphamide and 5-FU did not induce tumor regressions. The highest dose of the chemotherapeutic agent was the most effective in drug combinations. Histological analysis revealed a potentiation of the TNF-induced necrosis by cyclophosphamide. Increased hyperemia and extravasation of erythrocytes could be found in tumors of animals treated with the drug combination.

Cationic antigens are known to have considerable arthritogenic potential in experimental systems. During a systematic search for suitable, naturally occurring candidates an intracellular protein was isolated from the ribosomal pellet of Yersinia enterocolitica 0:3, a bacterial strain associated with reactive arthritis in humans. The protein is highly cationic, contains two 19-kD polypeptide chains linked by a disulfide bond, and reveals a strong tendency for spontaneous aggregation. It is suggested to be a nucleic acid binding protein. We tested this antigen for its ability to induce arthritis after intra-articular challenge in preimmunized rats. An acute inflammatory phase followed by transition to chronicity was observed both by technetium-99m scintigraphy and from histology. Massive polymorphonuclear leucocyte infiltration of the synovium was seen early on and fibrosis and thickening of the joint capsule occurred in later stages. Control groups showed no evidence of inflammation. Western blot and ELISA analysis of unselected sera from Yersinia enterocolitica 0:3-infected patients revealed antibodies to the antigen in the majority of cases, whereas healthy individuals rarely reacted. This is the first report of a naturally occurring cationic antigen capable of inducing immunologic tissue injury; it justifies the speculation that cationic antigens from prokaryotic cells could trigger reactive arthritis.in humans. (J. Clin. Invest. 1991. 87:632-642.)

Immunohistochemical investigation of 11 cardiac myxomas (CMs) including one malignant metastasizing CM showed a co-expression of epithelial (lu-5 and CAM 5.2), mesenchymal (vimentin) and neuroendocrine antigens (neuron-specific enolase) in all tumour cells. Factor VIII was found in the endothelial cells of capillaries only. In the subendocardium of fetal heart tissue close to the foramen ovale myofibroblasts reacting with the panepithelial antibody lu-5 were detected. We conclude that CMs are neoplasms that may develop from embryonic cell remnants.