Clinical significance of epithelial-to-mesenchymal transition in laryngeal carcinoma: Its role in the different subsites.

BACKGROUND: During epithelial-to-mesenchymal transition, cancer cells lose adhesion capacity gaining migratory properties. The role of the process on prognosis has been evaluated in 50 cases of laryngeal carcinoma. METHODS: E-cadherin, N-cadherin, ß-catenin, α-catenin, γ-catenin, caveolin-1, and vimentin immunohistochemical expression were evaluated using a double score based on staining intensity and cellular localization. RESULTS: Cytoplasmic E-cadherin and α/γ catenin staining were associated with a decrease in survival, cytoplasmic ß-catenin was associated with advanced stage, and N-cadherin and vimentin expression were associated with poor differentiation and tumor relapse. On the basis of cancer cells, epithelial or mesenchymal morphological and immunophenotypic similarity we identified 4 main subgroups correlated with a transition to a more undifferentiated phenotype, which have a different pattern of relapse and survival. CONCLUSION: The negative prognostic role of epithelial-to-mesenchymal transition has been confirmed and a predictive role in glottic tumors has been suggested, leading us to propose epithelial-to-mesenchymal transition as an additional adverse feature in laryngeal carcinoma.

Standard of care and promising new agents for triple negative metastatic breast cancer.

Triple negative breast cancer (TNBC) is a cluster of heterogeneous diseases, all of them sharing the lack of expression of estrogen and progesterone receptors and HER2 protein. They are characterized by different biological, molecular and clinical features, including a poor prognosis despite the increased sensitivity to the current cytotoxic therapies. Several studies have identified important molecular features which enable further subdivision of this type of tumor. We are drawing from genomics, transcription and translation analysis at different levels, to improve our knowledge of the molecular alterations along the pathways which are activated during carcinogenesis and tumor progression. How this information should be used for the rational selection of therapy is an ongoing challenge and the subject of numerous research studies in progress. Currently, the vascular endothelial growth factor (VEGF), poly (ADP-ribose) polymerase (PARP), HSP90 and Aurora inhibitors are most used as targeting agents in metastatic setting clinical trials. In this paper we will review the current knowledge about the genetic subtypes of TNBC and their different responses to conventional therapeutic strategies, as well as to some new promising molecular target agents, aimed to achieve more tailored therapies.

Involvement of the Src-cortactin pathway in migration induced by IGF-1 and EGF in human breast cancer cells.

Cancer cells need to become motile in order to escape the primary tumor and move to distant areas to form metastasis. They move as single cells or as a group, following different stimuli, including growth factors. Among them, insulin-like growth factor­1 (IGF-1) and epidermal growth factor (EGF) and their receptors have been implicated in the development and progression of human breast carcinoma. In this report, we provide evidence that the tyrosine kinase Src is responsible for migration promoted by both IGF-1 and EGF in MDA-MB-231 and MCF7 cells, although with a different effect. Moreover, both IGF-1 and EGF induce reorganization of actin cytoskeleton in lamellipodia and membrane ruffles in a time- and Src-dependent manner. Furthermore, we analyzed the tyrosine phosphorylation status of the actin-binding protein cortactin upon growth factor stimulation, showing that even the activation of cortactin is time- and Src-dependent. In addition, immunofluorescence analysis with anti-paxillin antibody reveals that, after treatment with growth factors, tyrosine phosphorylated cortactin is localized on the plasma membrane in correspondence of focal adhesions. Collectively, our findings suggest a crucial role for Src-mediated activation of cortactin in cell migration, reorganization of actin cytoskeleton and phosphotyrosine cortactin localization to the focal adhesions in human breast cancer cell lines upon both IGF-1 and EGF stimulation.

Neuroendocrine tumors of the gallbladder: a case report and review of the literature.

INTRODUCTION: Primary gallbladder neuroendocrine tumors are extremely rare, representing 0.2% of all neuroendocrine tumors. The diagnosis is incidental in most cases. CASE PRESENTATION: We describe the case of a 57-year-old Caucasian man who underwent laparoscopic cholecystectomy for the evaluation of a gallbladder polyp that had been incidentally detected by ultasonography. Histologically, his lesion was composed of monomorphic cells that contained small round nuclei and that were organized in small nodular, trabecular, and acinar structures. His cells were positive for chromogranin A and synaptophysin, and a diagnosis of "typical" carcinoid of the gallbladder was made. His post-operative computerized axial tomography, 111In-pentetreotide scintigraphy, and hormone-specific marker results were negative. He is disease-free 45 months after surgical treatment. CONCLUSIONS: Characteristic pathological findings of the gallbladder neuroendocrine tumors predict the prognosis. Whereas classical carcinoids of the gallbladder only rarely have a metastatic or invasive phenotype, the "atypical" variants are more aggressive and are associated with a poorer prognosis. Given the difficulty in distinguishing between benign and malignant lesions in the pre-surgical setting, we tend to consider each polypoid-like lesion of the gallbladder to be a high-risk lesion if it is larger than 1 cm and, as a result, to emphasize the need for cholecystectomy in all cases, relying on the pathological and immunohistochemistry analyses for the final diagnosis.

Somatostatin receptor scintigraphy in metastatic breast cancer patients.

The purpose of this study was to evaluate the efficacy of somatostatin receptor scintigraphy (SRS) in imaging metastases in patients with advanced breast cancer (BC), and assess the relationship between exposure to chemotherapy and hormonotherapy with overexpression of somatostatin receptor (SS-R) on the breast cancer cell surface. Twelve patients with metastatic breast cancer were intravenously (i.v.) injected with In-111 pentatreotide (120 MBq). Early and later images were obtained with a double-head gamma camera equipped with medium-energy collimators. SPECT was performed when needed. Imaging results were compared with computed tomography and bone scan. Uptake levels were evaluated by site-specific visual analysis. Metastatic breast cancer can be visualized with SRS. Global sensitivity of imaging was 80% and specificity for correct prediction of tumor absence was 100%. Sensitivity was significantly higher for bone and lung metastases. SRS results related to the expression of SS-R on metastatic cell surfaces did not evidence a relationship with the biologic characteristics of the primary BC and drug exposure. In our series, SRS quantitative analysis demonstrated that tumor metastases differ greatly in uptake levels. Fifteen percent of metastatic sites in our series showed strong uptake. Our data support the important specificity of SRS in identifying BC metastases, mostly in cases of bone and lung disease, as well as the role of SRS in predicting responsiveness of metastatic BC cells to treatment with somatostatin analogues (SS), when SS-Rs are overexpressed on cell surfaces. If our results are confirmed in large scale studies, SRS shows the potential to treat selected patients with overexpressed SS-R on their tumoral cells with designed target therapies with SS analogue.