Retinoic acid receptor ß2 (RARß2): nonivasive biomarker for distinguishing malignant versus benign prostate lesions from bodily fluids.

UNLABELLED: Alterations in the methylation patterns of promoter CpG islands have been associated with the transcriptional inhibition of genes in many human cancers, including prostate cancer (PCa). OBJECTIVES: The aim of our study was to evaluate the diagnostic value of aberrant promoter hypermethylation of retinoic acid receptor ß2 (RARß2) gene in serum DNA samples from patients with the diagnosis of PCa and benign prostatic hyperplasia (BPH), as a new epigenetic biomarker in distinguishing between malignant and non-malignant lesions. MATERIALS AND METHODS: Aberrant promoter hypermethylation was investigated in genomic DNA isolated from the serum of 91 patients diagnosed with of PCa and 94 with BPH (control subjects). In order to evaluate the methylation status of the RARß2 gene we used the quantitative methylation-specific PCR (QMSP) method. RESULTS: Promoter hypermethylation of RARß2 gene was detected in serum samples from 89 of 91 (92.86%) patients with PCa, and in 10 of the 94 (10.7%) patients with BPH. CONCLUSIONS: RARß2 represents a promising molecular biomarker which may be used in discriminating between malignant and benign prostatic diseases by noninvasive methods.

Correlation between histopathological form and the degree of neuroendocrine differentiations in prostate cancer.

Prostate cancer (PCa) is the most frequent neoplasic condition in males, but only 64-65% of the cases are sensitive to hormone therapy. The aim of this study was to investigate the neuroendocrine component of the prostatic carcinoma, in relation to the histopathological form and the degree of differentiation. Biopsies were obtained through transurethral resection, from 82 patients with prostate cancer. In order to assess the histopathological form and the Gleason score, one section from each case was stained with Hematoxylin-Eosin. Additional sections were stained with chromogranin A. We considered neuroendocrine cell hyperplasia to have a higher value than that observed in benign prostatic hyperplasia (BPH) and normal prostate (over three neuroendocrine cells÷gland). The quantification of neuroendocrine differentiation (NED) has been significant; the reaction was considered to be weak (2-10% neuroendocrine cells), moderate (10-20%) and intense (over 50%). Cells positive for chromogranin A have been identified in all the cases, but a larger number than that registered in normal tissue has been noted in 59 patients (71.95%). In most of the cases, the neuroendocrine cells have been distributed in small groups among the neoplasic cells, and rarely isolated. In two cases of small cell carcinoma most of the tumoral cells have been positive for chromogranin A. In conclusion, the study of neuroendocrine differentiation in patients with prostatic carcinoma revealed hyperplasia of positive chromogranin A cells, in 71.95% of cases. Neuroendocrine prostatic differentiation is correlated with the advanced stage of evolution and possibly with the resistance to hormonal treatment.

Genetic and epigenetic biomarkers for early detection, therapeutic effectiveness and relapse monitoring in bladder cancer.

Urinary bladder cancer is the fifth most common cancer in the Western world and is responsible for about 3% of all cancer-related deaths. Because most advanced invasive or metastatic cancers have low cure rates, risk assessment and early detection of the clinically occult premalignant phases of neoplasia are a particular importance. Many tumor biomarkers for bladder cancer have been evaluated for use in detecting and monitoring bladder cancers tissue specimens, bladder washes, and urine specimens but, none of the biomarkers reported to date has shown sufficient sensitivity and specificity to detect the entire spectrum of bladder cancers in routine clinical practice. The limitations of established prognostic markers requires us to identify better molecular parameters that could be of interest in predicting the prognosis of bladder cancer patients, in particular, the high-risk patient groups that are at risk of progression and recurrence. Methylation is an important molecular mechanism in the development of bladder cancer and could be used as a prognostic and diagnostic biomarker, because hypermethylation of several gene promoters was detected in urine sediment DNA from bladder cancer patients. Aberrant patterns of epigenetic modification could be, in the near future, crucial indicators in cancer diagnosis, prognosis, and additionally could be good targets for developing novel therapies while maintaining quality of life.

Urine cytology in the follow-up of patients with transitional cell carcinoma of the urinary bladder: is that enough as a single method?

There were studied 130 patients with Ta, T1 and T2 transitional cell carcinomas of the urinary bladder, all treated by transurethral resection. After transurethral resection the follow-up was performed in 48 cases by cystoscopy and urine cytology and in 82 cases by cytology alone. In the first group there were 27 recurrences; cystoscopy failed to identify recurrences in 3 cases and cytology in one of them; all 3 patients with apparently false positive cytology recurred at 4, 9 and 11 months from the cytodiagnosis. From 82 patients of the second group 42 developed recurrences. Urine cytology was positive in 80.9%, suspect in 14.2% and false negative in 4.7% of cases. There were only 2 unsuspected recurrences with a consecutive delay in the correct diagnosis of recurrence in another one. Our results suggest that urine cytology can replace cystoscopy only when it exists a good correlation between its results with pathological findings (over 80% real positive results).

Cytologic diagnosis of transitional cell carcinoma of the urinary bladder. Comparison with endoscopical and pathological findings on 538 cases.

There were investigated 583 cases with tumors of the urinary bladder and 612 patients with non-malignant diseases of the urinary tract. Samples of voided urine were taken from all cases and direct smears fixed by drying were stained by rapid blue polychrome-tanin Dragan method Cytological results were compared with endoscopical and pathological findings. The overall rate of real positive results was 91.7% and false negative results were noticed in 8.3% of cases. A direct relationship between real positive results and histological "G" was found. Causes for false negative results were: tumor developed in a bladder diverticulum, calcified tumor, irradiated tumor, insufficient quantity of voided urine, chronic urinary infections and underestimation of cytological criteria of cellular malignancy. There were 9 false positive results in patients with nonmalignant diseases, due to lithiasis, chronic renal failure and chronic urinary infections. The cytological grade of differentiation was performed by the method purposed by Friedman and Ash, and concordance with the standard histological finding was 76.4%. Urine cytology is thought to be a useful method in the primary diagnosis and recurrences of transitional cell carcinoma of the urinary bladder, in all patients with hematuria, recurrent infections of the urinary tract and neglected lithiasis.