[Expression levels of the IAP antagonists XAF1, Smac/DIABLO and HtrA2 in testicular germ cell tumours]. / Expression der pro-apoptotischen Apoptoseinhibitor-(IAP)Antagonisten XAF1, Smac/DIABLO und HtrA2 in Keimzelltumoren des Hodens.

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.

[New polymorphisms in the PSA promoter in patients with prostate carcinoma]. / Neue polymorphismen im PSA-promoter bei prostatakrebs.

INTRODUCTION: PSA is still the most important parameter in the diagnosis and follow-up of prostate cancer. We searched for single nucleotide polymorphisms (SNP) in four different parts of the PSA promoter, which harbour binding sites for major transcriptional regulators using PCR-based combined SSCP and sequence analysis. MATERIALS AND METHODS: Lymphocyte DNA samples from 279 prostate cancer patients and 55 age-matched controls were subjected to SSCP analysis after PCR amplification of four approximately 200-bp fragments selected to contain the known AREs I-III or the transcriptional start site, respectively. Conspicuous PCR fragments with variant SSCP patterns were subsequently cloned and sequenced. Computer-assisted comparison with published sequences of the promoter region was performed to reveal polymorphic sites. RESULTS: In 66.6 % of the carcinoma cases DNA displayed polymorphisms in ARE I-, whereas the benign cases showed this SNP only in 14.5 %. This difference was highly significant (p < 0.0001). In addition, we found novel SNPs with lower frequency at positions - 179, - 230, - 233 (ARE I) and - 356 (ARE II). CONCLUSION: The present study confirmed that the otherwise already described polymorphism in the position - 158 is highly significantly more frequent in prostate cancer patients than in the control group. There is no significant correlation to the clinical stage of the disease. Furthermore we described for the first time four rare, previously unknown polymorphisms.