Intracardiac chloroma.

Chloromas are not frequently seen in patients with acute myelogenous leukemia and chloromas involving cardiac structures have only been rarely reported in the literature. We report a complete radiographic response to low-dose fractionated radiotherapy in a patient with an intracardiac chloroma.

Expression of the translation initiation factors eIF-4E and eIF-2* is frequently increased in neoplastic cells of Hodgkin lymphoma.

The rate of protein synthesis is regulated in part by 2 key translation initiation factors, eIF-4E and eIF-2*. The expression and activity of both factors are increased transiently when normal resting cells are stimulated to proliferate, but they are constitutively elevated in oncogene-transformed cultured cells. Overexpression of either initiation factor induces a tumorigenic phenotype in rodent cells. We have shown earlier that expression of both eIF-4E and eIF-2* is increased in non-Hodgkin lymphomas (non-HLs). In this study, we performed an immunohistochemical survey of these translation initiation factors in neoplastic cells of HL. We also used Western blot to addressed the possibility that eIF-4E increases expression of NFkappaB. Our results indicate that both eIF-4E and eIF-2* are strongly expressed in neoplastic cells of HL in most cases examined as compared with weak or undetectable expression in most surrounding lymphocytes. An increase in eIF-4E expression may lead to constitutively high expression of NFkappaB, a transcription factor implicated in resistance to apoptosis and induction of cytokine gene expression in various cells, including neoplastic cells of HL.

The role of translation in neoplastic transformation from a pathologist's point of view.

Increased cell proliferation, which is a hallmark of aggressive malignant neoplasms, requires a general increase in protein synthesis and a specific increase in the synthesis of replication-promoting proteins. Transient increase in the general protein synthesis rate, as well as preferential translation of specific mRNAs coding for growth promoting proteins (e.g. cyclin D1), takes place during normal mitogenic response. A number of extensively studied growth signal transduction pathways (Ras, PI3K, MAPK, mTOR-dependent pathways) activate the function and expression of various components of the translational machinery. In abnormal situations, constitutive activation of signal transduction pathways (e.g. oncogenic activation of Ras or Myc) leads to continuous upregulation of key elements of translational machinery. On the other hand, tumor suppressor genes (p53, pRb) downregulate ribosomal and tRNA synthesis, and their inactivation results in uncontrolled production of these translational components. During recent years, a significant effort has been dedicated to determining whether expression of translation factors is increased in human tumors using clinical biopsy specimens. The results of these studies indicate that expression of particular translation initiation factors is not always increased in human neoplasms. The pattern of expression is characteristic for a particular tumor type. For example, eIF-4E is usually increased in bronchioloalveolar carcinomas but not in squamous cell carcinomas of the lung. Interestingly, in certain highly proliferative and aggressive neoplasms (e.g. squamous cell carcinoma of the lung, melanoma), the expression of eIF-4E is barely detectable. These findings suggest that mechanisms for increasing general protein synthesis in various neoplasms differ significantly. Finally, the possibility of qualitative alterations in the translational machinery, rather than a simple increase in the activity of its components, is discussed along with the possibility of targeting those qualitative differences for tumor therapy.

Expression of translation initiation factor eIF-2alpha is increased in benign and malignant melanocytic and colonic epithelial neoplasms.

BACKGROUND: Stimulation of resting cells by growth factors leads to an increase in the rate of protein synthesis, which is necessary for cell growth and division. Translation initiation factor eIF-2alpha is one of the key translation factors mediating the effects of growth factors on protein synthesis. In normal cells, expression of eIF-2alpha is increased transiently, but its levels are elevated constitutively in oncogene-transformed cells. Overexpression of constitutively active eIF-2alpha in rodent cells makes them tumorigenic. In this article, the authors report their findings on the increased expression of eIF-2alpha in human benign and malignant neoplasms originating from melanocytes and colonic epithelium. METHODS: Immunohistochemistry was used to analyze the expression of eIF-2alpha, eIF-4E, and cyclin D1 in melanocytic nevi and melanomas and the expression of eIF-2alpha in colonic adenomas and carcinomas. RESULTS: The authors found that the expression of eIF-2alpha was increased markedly in both benign and malignant neoplasms of melanocytes and colonic epithelium. CONCLUSIONS: Increased expression of eIF-2alpha took place in both benign and malignant neoplasms of melanocytes and colonic epithelium. These findings suggest that elevated expression of this translation initiation factor may contribute to tumor initiation and progression but that it is not sufficient for establishing a malignant phenotype in the tumors analyzed in this study.