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Abstract  Ezrin is a cytoskeleton linker protein that is actively involved in the metastatic process of cancer cells. We have recently reported that ezrin expression in conventional osteosarcoma was an independent prognostic factor for event-free survival and overall survival. In this work, ezrin expression was found in all histological subtypes. Especially cartilaginous areas in chondroblastic osteosarcomas were immunopositive for ezrin. We wanted to know if ezrin could be a useful diagnostic marker in bone pathology. We have searched for ezrin expression in 208 cartilaginous tumours by immunohistochemistry and in 16 chondroblastic osteosarcomas. All conventional chondrosarcomas, whatever their grade, were negative, while ten of 16 chondroblastic osteosarcomas were positive. In contrast, dedifferentiated (five of 14) and mesenchymal chondrosarcomas (five of ten) showed ezrin positivity. Some chondroblastomas and more rarely chondromyxoid fibromas also exhibited ezrin expression. These data suggest that ezrin is a useful immunohistochemical marker for differential diagnosis between chondroblastic osteosarcomas and conventional chondrosarcomas with a specificity of 100%. Ezrin expression in dedifferentiated and mesenchymal chondrosarcomas which are aggressive neoplasms resistant to conventional treatment means that ezrin could be a therapeutic target. Ezrin expression in chondroblastomas is more intriguing and requires further study to assess prognostic value. [ABSTRACT FROM AUTHOR]

In 20 sex-cord tumors of the testes, we investigated immunohistochemistry as a possible method for histopathological diagnosis and evaluation of prognosis. We examined the following molecules: inhibin, CD99, cytokeratin, vimentin, MIB-1, estrogen receptors and progesterone receptors. These tumors of the testes comprised 18 Sertoli cell tumors (ScT) and two undifferentiated sex-cord tumors (USCT). Four tumors have been considered as malignant, because of metastatic spread. Inhibin was expressed by the tumor cells in 80% of sex cord tumors, without any correlation to the degree of differentiation and only in 25% of the malignant cases. Inhibin is a specific marker for sex-cord tumors of the testis and is particularly useful for the diagnosis of USCT. CD99, vimentin, keratin, progesterone and estrogen receptors were expressed in, respectively, 60%, 75%, 35%, 65% and 20% of cases; 95% expressed one of the three following markers: inhibin, CD99 or vimentin. Proliferation index MIB-1 was equal to or higher than 30% in the four malignant cases versus less than 20% in other cases. Lack of inhibin expression and a proliferation index (MIB-1) greater than 30% should be considered as a criterion in favor of malignancy. [ABSTRACT FROM AUTHOR]

Specific treatments targeted toward oncogenes expressed in cancer cells are currently under development. Patients with urothelial carcinomas showing HER-2/ neu (human epidermal growth factor receptor 2) overexpression are candidates for such a specific treatment (trastuzumab). However, to be effective, this therapeutic approach requires an extremely reliable evaluation of HER-2/ neu status in tumors. In order to assess the status of expression of this gene and to optimize its assessment, we analyzed a series of 64 primary urothelial carcinomas using immunohistochemistry (IHC) with the CB11 monoclonal antibody coupled with fluorescent in situ hybridization (FISH) in 21 cases. Strong HER-2/ neu overexpression was detected using IHC in 15 of the 64 (23%) cases analyzed, and this rate rose to 33% for patients with metastases. HER-2/ neu overexpression, as revealed using IHC, is strongly associated (95%) with gene amplification assessed using FISH. Patients with urothelial carcinomas overexpressing HER-2/ neu using IHC are potential candidates for targeted chemotherapy. [ABSTRACT FROM AUTHOR]

Murine models have shown that IL-18 has antiangiogenic and antitumor effects, but little is known about IL-18 production in human tumors. We investigated IL-18 expression in clinically localized prostate cancers by immunohistochemistry and showed that 75% of the prostate cancers studied (27/36 cases) presented with tumor cells producing IL-18. Prostate tumor cell lines PC-3, DU 145 and LNCaP synthesized the immature form of IL-18 (p24). IFN-γ produced in prostate cancers induced caspase-1 mRNA and IL-18 secretion of tumor cell lines, which was inhibited by the cell-permeable Tyr-Val-Ala-Asp-aldehyde caspase-1 inhibitor (YVAD-CHO). Interestingly, IFN-α also induced IL-18 secretion of the poorly differentiated cell line PC-3. PC-3 and DU 145, but not the well-differentiated cell line LNCaP, expressed IL-18Rα (IL-1Rrp) protein and transcripts for IL-18Rβ (AcPL). Exogenous IL-18 increased mitochondrial activity of both cell lines evaluated by the tetrazolium (MTT) assay but did not influence their proliferation. This indicated that prostate tumor cells could secrete IL-18 in response to IFN-γ in the tumor microenvironment and that IL-18 could act as a autocrine/paracrine factor for the tumor. In the cohort of patients studied, IL-18 expression in prostate cancers (with up to 10% of tumor cells stained) was associated with a favorable outcome and equally predictive as pathologic stage on multivariate analysis (log rank test, p = 0.02). Tumor IL-18 production is a novel physiopathologic feature of prostate cancer and appears to be a favorable event in the course of the disease. Modulation of IL-18 production by interferons could have a beneficial clinical effect, which deserves further investigation. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]