Molecular Pathology of Thymic Epithelial Neoplasms

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The etiology and molecular pathogenesis of thymic tumors are unknown. However, during the last two decades there has been some progress on elucidating the genetic abnormalities present and molecular pathways altered in thymic tumors. These abnormalities, while bearing distinctions and similarities to those described in other tumors, can be organized under the “hallmarks of cancer,” as proposed by Hanahan and Weinberg. These changes include self-sufficiency in growth signaling, insensitivity to antigrowth signals, ability to evade apoptosis, limitless replicative potential, ability to sustain angiogenesis, and tissue invasion and metastasis. However, this progress is still limited and has not led to better tumor classifications, prognostication of outcome, and design of molecular targeted therapy.

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Clinico-Pathologic Features of Thymic Tumors

Thymoma classification has been a challenging field in pathology because of the wide heterogeneity of these tumors from the viewpoint of pathology, clinical characteristics, and prognosis. The so-called “histogenic” classification, which tried to reflect the major functional and anatomic compartments of the thymus, distinguished medullary, mixed, predominantly cortical and cortical thymomas, and well-differentiated thymic carcinoma [10], [11], [12], [13]. In 1999, the World Health Organization

Molecular Pathogenesis of Thymic Tumors

Currently, there is widespread acceptance that the neoplastic transformation of normal epithelial cells represents a multistep accumulation of genetic and epigenetic alterations, including abnormalities for the activation of oncogenes and inactivation of tumor suppressor genes (TSG). While oncogenes and TSGs are required for normal cell proliferation and differentiation, their aberrant expression leads to abnormal cell proliferation and tumor development. Oncogenes have a role in signal

Molecular Profiling Studies in Thymic Epithelial Tumors

There is a belief that the pathogenesis and behavior of individual thymic tumors cannot be completely understood through the analysis of individual or a small number of genes. Recently, the use of molecular global profiling technologies, including DNA, cDNA microarrays, and proteomics-based analyses, has led to a significant number of exciting new biologic discoveries and important correlations between gene and protein expression patterns and disease states in several human cancers. In thymic

Summary

Although the etiology of thymic epithelial tumors is unknown, during the last two decades there has been progress in elucidating some genetic abnormalities present and molecular pathways altered in these tumors (Table 1). These abnormalities, while bearing distinctions and similiarities to those described in other tumors, can be organized under the “hallmarks of cancer,” as proposed by Hanahan and Weinberg [17] (Fig. 1). However, this progress is still meager and has not led to better tumor

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