Search

In recent years the classification of pulmonary cancer has seen a paradigm shift with respect to both morphological as well as molecular aspects. On the morphological side this includes novel criteria for tumor classification from biopsy material based on morphological and immunohistochemical aspects as well as a novel classification based on morphological patterns for pulmonary adenocarcinomas. In addition, this new classification now includes adenocarcinoma in situ as well as minimally invasive adenocarcinoma as novel entities and a variety of novel adenocarcinoma subtypes. This reclassification was accompanied and complemented by tremendous developments in the field of lung cancer genomics which paved the way for now widely established predictive molecular markers, e.g. epidermal growth factor receptor (EGFR) mutations and EML4-ALK translocations and will certainly lead to a variety of novel predictive markers not only for pulmonary adenocarcinoma but also for other pulmonary neoplasms.

Prostate cancer is a common and clinically heterogeneous disease. Understanding the biology of prostate cancer is necessary to best determinate the risk of disease progression and develop novel therapeutic approaches to prevent or slow down disease progression. The recent discovery and subsequent characterization of recurrent gene rearrangements of ETS genes - most frequently ERG - in the majority of prostate cancers is a milestone in translational prostate cancer research. Although multiple molecular alterations have been detected in prostate cancer, a detailed understanding of gene fusion in prostate cancer should help explain the clinical and biologic diversity in addition to providing a rationale for a molecular sub-classification of the disease. This review describes the path from the identification of common ETS gene rearrangements in prostate cancer to possible applications in the treatment of patients, on to the potential scientific implications arising from their discovery.

Purpose: Down-regulation of the IAP antagonistis XAF1, Smac/DIABLO and HtrA2, has been related to the onset and progression of various malignancies. We examined the mRNA-expression of these pro-apoptotic parameters in testicular germ cell tumors (TGCT) and normal testicular tissue and correlated their expression levels to clinicopathological tumour features., Material and Methods: Real-time RT-PCR was used to quantify the mRNA-expression of XAF1, Smac/DIABLO and HtrA2 in normal testicular tissue (n = 18), carcinoma in situ (n = 4), seminomas (n = 64), and non-seminomatous germ cell tumors (n = 35)., Results: Compared to normal testicular tissue, the expression levels of XAF1 were increased in TGCT (p < 0.001), whereas those of Smac/DIABLO and HtrA2 were decreased (p < 0.001 and p < 0.001). Smac/DIABLO expression levels showed a significant trend towards a gradual decrease from normal testicular tissue to CIS and seminomas and finally to NSGCT (p < 0.001). Moreover, XAF1 and HtrA2 expression levels gradually increased with progression of clinical tumour stage in seminoma patients (p = 0.001 and p = 0.018), their expression levels being strongly intercorrelated (Spearman rho correlation coefficient: 0.674; p < 0.001)., Conclusion: These data suggest that a down-regulation of Smac/DIABLO and HtrA2 is implicated in the development and progression of TGCT, whereas overexpression of XAF1 in TGCT might contribute to their extraordinary sensitivity to chemotherapy. Regarding the additional correlation of XAF1 and HtrA2 expression with clinical tumour stage in seminoma patients, it appears reasonable to further evaluate these three IAP antagonists as molecular parameters for the prediction of treatment response and prognosis of TGCT patients.

Background: Recurrent chromosomal rearrangements have not been well characterized in common carcinomas. Using a novel bioinformatics approach, our group recently described a novel gene fusion in PCa. This fusion involves the androgen-regulated gene TMPRSS2 and so far three members of the ETS family of transcription factors already described as rearranged in the Ewing's family of tumors. By analogy, fusion status in prostate cancer may determine clinical outcome and secondary genetic alterations as witnessed in Ewing's tumors., Material: These novel gene fusions occur in the majority of prostate cancers identified by PSA screening and are the driving mechanism for overexpression of the three members of the ETS transcription factor family, either ERG (21q22.3), ETV1 (7p21.2), or ETV4 (17q21). Considering the high incidence of prostate cancer and the high frequency of this gene fusion, the TMPRSS2-ETS gene fusion is the most common genetic aberration so far described in human malignancies., Results: So far, this is the only gene rearrangement in any of the most prevalent cancers. As confirmed by other groups, we demonstrated that, within the group of ETS transcription factors, ERG is the most common fusion partner of the ETS genes with TMPRSS2. This gene fusion is considered to be an early event in PCa development. Emerging data suggest that gene fusion PCa demonstrates a distinct clinical course and thus support its use as a diagnostic test and prognostic biomarker. Also similar to the Philadelphia chromosome in chronic myelogenous leukemia (CML), the gene fusion in prostate cancer has potential as an important candidate for the development of targeted therapy.