Detection of TMPRSS2-ERG fusion gene in benign prostatic hyperplasia.

The Ets-related gene fusions are among the most common molecular alterations in prostate cancer (PCa) and are detected in more than 50 % of PCas. Transmembrane protease serine 2 and Ets-related gene fusion (TMPRSS2-ERG) is the most frequently identified chimeric gene and has been associated with undifferentiated and invasive phenotypes. TMPRSS2-ERG has also been detected in prostate intraepithelial neoplasia (PIN) lesions and more rarely in benign prostatic hyperplasia (BPH) regions mainly in PCa-bearing glands. The possibility that the fusion TMPRSS2-ERG may be present in BPH samples in the absence of apparent PCa was addressed. Out of 115 BPH samples, three were found positive employing RT-PCR. The presence of the fusion gene was confirmed by FISH for these samples, and an additional four samples were found to carry the TMPRSS2-ERG fusion out of 43 tested by the later approach. The presence of the TMPRSS2-ERG fusion did not result in altered expression of 12 putative downstream targets. These findings indicate that TMPRSS2-ERG may or may not lead to PCa development.

The prognostic importance of the morphological subdivision of the grade II superficial bladder cancer.

UNLABELLED: In this study a morphological subdivision of grade (g)II superficial bladder cancer is proposed and correlated with recurrence and progression rate. Forty patients, 33 males and 7 females, of 70 years mean age, with initial gII superficial transitional bladder cancer were treated with transurethral resection between January and December 1987 with follow-up for a mean period of 4 years. Recurrences were observed in 24 patients. All histological specimens were reviewed and reclassified to gIIa and gIIb mainly according to the variation in nuclear size, the degree of nuclear atypia and the number of mitoses. 42.1% (8/19) of the gIIa and 76.2% (16/21) of the gIIb tumors recurred. The observed difference in recurrence rate was statistically significant (s.s)-p < 0.05. The disease-free interval after the initial presentation was over two years in 50% (4/8) of gIIa and in 6.25% (1/16) of gIIb patients (s.s. difference-p < 0.05). None of the patients with gIIa, but 37.5% (6/16) with gIIb urothelial cancer had more than two recurrences (s.s. difference-p < 0.05). All gIIa recurred as gIIa superficial cancers, 62.5% (10/16) of gIIb as gIIb (5 superficial and 5 invasive) and the remainder 37.5% (6/16) as invasive gIII tumors. Only one patient with repeated recurrences died two years after the initial presentation. 3 patients died from other causes. IN CONCLUSION: 1. The morphological subdivision of gII urothelial cancer into gIIa and gIIb has a prognostic significance, as it is related to the recurrence rate, the disease-free interval after the initial resection, the number of recurrences and the progression rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic significance of matrix metalloproteinases 2 and 9 in bladder cancer.

BACKGROUND: The levels of matrix metalloproteinases MMP-2 and MMP-9 (type IV collagenases), which degrade the extracellular matrix of the basement membrane, were evaluated as prognostic indicators of metastasis in urothelial carcinoma. MATERIALS AND METHODS: Quantitative gel zymography and immunohistochemistry were used and compared with clinical data at the follow-up period of 36 months. RESULTS: Zymographical analysis of the levels of MMP-9 and active MMP-2 showed a statistically significant increase with tumor grade and invasiveness. This correlation was confirmed by immunohistochemical analysis of MMP-9 expression. However, the correlation between the levels of both gelatinases with recurrence in superficial tumours or progression in invasive tumours was not statistically significant. CONCLUSION: MMPs may have an important role in the invasion mechanism of urothelial cancer and could be useful prognostic markers for patients with bladder carcinoma. The relationship between MMP-2 and MMP-9 expression and the metastatic potential of bladder carcinoma needs further evaluation in subsequent clinical studies.