No abstract

In this in vitro model, FTI and LSI predicted RF lesion dimensions, whereas power and CF did not. The LSI predictive value was higher than that of FTI. Steam pops occurred only using high ablation power levels, regardless of the targeted LSI.

Cholangiocarcinoma (CCA) carries a severe prognosis because of its strong invasiveness and early metastasization. In several patients, otherwise eligible for surgical resection, micrometastasis are already present at the time of surgery. The mechanisms responsible for CCA invasiveness are unclear. S100A4, a member of the S100 family of small Ca2+-binding proteins, is expressed in mesenchymal cells, regulates cell motility in several cell types, and is expressed in some epithelial cancers. Thus, we aimed to study the role of S100A4 in CCA invasiveness and metastasization. The expression of S100A4 was studied by immunohistochemistry in 93 human liver samples of CCA patients undergoing surgical resection and correlated with metastases development (67 cases) and patient survival following surgery using log rank tests and multivariate analysis. S100A4 expression was studied in EGI-1 and TFK-1, human CCA cell lines with and without nuclear S100A4 expression, respectively. Metastatic properties of CCA cells were assessed by xenotransplantation in severe combined immunodeficiency (SCID) mice after transduction with lentiviral vectors encoding firefly luciferase gene. Proliferation, motility (wound healing), invasiveness (Boyden chamber), and metalloproteinases (MMPs) secretion were studied in CCA cells, with or without lentiviral silencing of S100A4. Nuclear expression of S100A4 by neoplastic ducts was a strong predictor of metastasization and reduced survival after resection (P < 0.01). EGI-1 CCA cells showed stronger metastatic properties than TFK-1 when xenotransplanted in SCID mice. S100A4-silenced EGI-1 cells showed significantly reduced motility, invasiveness, and MMP-9 secretion in vitro, without changes in cell proliferation. Conclusion Nuclear S100A4 identifies a subset of CCA patients with a poor prognosis after surgical resection. Nuclear expression of S100A4 increases CCA cells invasiveness and metastasization, indicating that S100A4 may also represent a potential therapeutic target.

FLI-1 nuclear transcription factor has been proposed as a useful tool in the differential diagnosis of small round cell sarcomas. Recently, FLI-1 has been reported as the first nuclear marker of endothelial differentiation. However, its clinical use has been hampered by major interpretation problems, due to the presence of background staining as well as staining variation between different lots of the same antiserum. In this study, a novel monoclonal antibody raised against the carboxyl terminal of the FLI-1 protein (clone GI146-222, BD Pharmingen) was tested in a series of small round cell and vascular neoplasms. Furthermore, in order to assess FLI-1 specificity, we analyzed its expression in a series of common epithelial and nonepithelial malignancies. In total, 15 Ewing's sarcomas, 10 rhabdomyosarcomas, 5 desmoplastic small round cell tumors, 10 synovial sarcomas, 10 high-grade pleomorphic sarcomas, 10 malignant melanomas, 5 Merkel's carcinomas, 10 colonic adenocarcinomas, 10 breast carcinomas, 10 lung adenocarcinomas, 20 angiosarcomas, 5 epithelioid hemangioendotheliomas, 10 Kaposi's sarcomas and 10 benign hemangiomas, were stained. A strong FLI-1 immunoreactivity was detected in all Ewing's sarcomas and vascular neoplasms, highlighting the high sensitivity of FLI-1 monoclonal antibody. However, 2/5 Merkel's carcinomas and 1/10 malignant melanomas showed a strong nuclear immunostaining, suggesting that FLI-1 may not be so helpful in the differential diagnosis of cutaneous Ewing's sarcoma. In addition, a weak immunoreactivity was found in 3/5 Merkel cell carcinomas, 3/10 synovial sarcomas, 5/10 malignant melanomas, 6/10 lung adenocarcinomas and in 1/10 breast carcinomas. In contrast, all the rhabdomyosarcomas, desmoplastic small round cell tumors, high-grade pleomorphic sarcomas and colonic adenocarcinomas tested were negative. Importantly, in contrast with previous studies, no background staining was observed. Our results indicate that FLI-1 monoclonal antibody can be reliably applied to the differential diagnosis of small round cell neoplasms of soft tissue, and confirm its important role as nuclear marker of endothelial differentiation, mainly helpful in those cases in which technical artifacts are seen by using the traditional membranous and cytoplasmic endothelial markers. 2 The EWS/FLI-1 chimeric protein binds DNA with the same affinity as FLI-1, but EWS/FLI-1 transcriptional activation of the target genes is much more efficient.3 ES/PNET belongs to a heterogeneous group of mesenchymal neoplasms featuring round cell morphology and therefore collectively known as small round cell sarcomas. Alveolar rhabdomyosarcoma (RMS), desmoplastic small round cell tumor (DSRCT), mesenchymal chondrosarcoma and poorly differentiated synovial sarcoma (SS) also belong to

Rabbit monoclonal antibodies (RabMAbs) represent a novel category of immunoreagents that may combine the best properties of both mouse monoclonal antibodies (MMAs) and of rabbit antisera. In the attempt to verify the performance of this new class of antibodies on paraffin-embedded tissue, RabMAbs against estrogen receptor, progesterone receptor, Ki-67, cyclin D1, CD3, CD5, CD23, and synaptophysin were tested on several tumor types as well as normal tissues. The results were compared with those obtained with classic MMAs against the same antigens. RabMAbs appear to offer increased sensitivity with no apparent loss of specificity. On routine use they permit higher working dilutions (5 to 10 times on average), allowing significant improvement in terms of laboratory efficiency. The robustness of RabMAbs is further proved by the fact that in some instances optimal staining can be obtained even without antigen retrieval. In consideration of the high performance observed, routine use of RabMAbs may contribute significantly to standardize diagnostic immunohistochemical procedures.