Potential clinical applications of microRNAs as biomarkers for renal cell carcinoma.

INTRODUCTION: Renal cell carcinoma (RCC) accounts for 3% of adult malignancies and more than 90% of kidney neoplasms. High rates of undiagnostic percutaneous kidney biopsies and difficulties in reliable pre-operative differentiation between malignant and benign renal tumors using contemporary imaging techniques result in large numbers of redundant surgeries. Absence of specific biomarkers for early detection and monitoring complicates on-time diagnosis of the disease and relapse. For the patients followed up after having a nephrectomy, a noninvasive and sensitive biomarker enabling early detection of disease relapse would be extremely useful. MATERIAL AND METHODS: The study is a review of recent knowledge regarding potential clinical applications of microRNAs (miRNAs) as biomarkers of RCC. RESULTS: MicroRNAs are essential regulators of various processes such as cell proliferation, differentiation, development and death; they have been implicated in diverse biological and pathological processes in RCC. There is a class of miRNAs that promote RCC development (oncomirs) and a class of miRNAs that negatively regulate oncogenes, suppress tumor growth and invasion, and thus could be considered treatment agents (anti-oncomirs). Separate miRNAs and specific miRNAs expression profiles have been identified, enabling early detection of the disease, prediction of response to systemic therapy, or prognostication of biological behavior of the disease. CONCLUSIONS: The miRNA network analysis and gene profiling may help to identify the most sensible molecular signatures of RCC that can be used for diagnostic purposes, as well as poor prognosis signatures and poor therapeutic response signatures in patients who undergo systemic therapy.

Should all specimens taken during surgical treatment of patients with benign prostatic hyperplasia be assessed by a pathologist?

INTRODUCTION: In some patients submitted to transurethral resection of the prostatic (TURP) or prostatectomy (OAE) due to benign prostate hyperplasia (BPH), pathological evaluations (PE) revealed coexistence of prostate cancer (PCa) and BPH. The aim of the study is to evaluate the incidence of PCa diagnosed incidentally in prostate specimens taken during BPH surgery, to assess the need of routine PE and to define the group of patients in whom PE could be abandoned without the risk of omitting clinically significant PCa. MATERIAL AND METHODS: 968 consecutive men were subjected to surgical treatment due to BPH in Jan. 2004-Sep. 2010. RESULTS: 823 (85%) underwent TURP and 145 (15%) OAE. Incidental (Inc) PCa was diagnosed in 34(3.5%) pts. T1a and T1b stages were determined in 19 (2%) and 15 (1.5%) cases. Preoperative prostate biopsy due to abnormal prostate specific antigen (PSA) or digital rectal exam (DRE) was performed in 85 (8.8%) pts. Of PCa pts, 7 (20.58%) had undergone a cancer negative biopsy preoperatively. In BPH pts, 78 (8.35%) had undergone a prostate biopsy previously (p <0.01). Univariate and logit regression analyses had not revealed any correlations between age, Pv, serum PSA and frequency of IncPCa. The difference in rate of PCa diagnosed in patients with PSAD ≥0.15 and <0.15 was 8 pts (14.04%) and 20 pts (4.05%), respectively (p <0.001). Gls in those pts was >6 only in 4 cases. CONCLUSIONS: Despite the fact of low PCa detection rate observed in our study, this condition was clinically relevant in 15 (1.5%) subjects. It is difficult to establish any cut off values of pts' age, Pv, serum PSA level suggestive of negligible risk for prostate cancer.

Should active surveillance in prostate cancer patients be based on a single histological assessment?

INTRODUCTION: Active surveillance (AS) is always associated with a degree of uncertainty, whether or not prostate biopsy (TRUSBx) results indeed can be relied on for evaluation of cancer stage and histological grade, as the most commonly observed limitations of TRUSBx are undergrading, understaging and underestimating true prostate cancer (PCa) volume. We evaluated prostate cancer characteristics in men who could have been offered active surveillance based on clinical features and TRUSBx results, and compared them with the same patient's histology results following their radical prostatectomy (RP). Moreover, we assessed the level of consistency in reporting TRUSBx and RP specimens by the same pathologist on two separate occasions, as well as by another independent pathologist. MATERIAL AND METHODS: All patients who underwent RP between 2005 and 2008 had their medical records reviewed retrospectively. All histological specimens were prospectively re-evaluated by the same pathologist, as well as by a second to assess for intra- and interobserver variability, respectively. RESULTS: Eight out of a total of 124 patients who underwent RP could have been offered AS on the basis of initial microscopic reports. However, there was significant intra- and interobserver variability. The differences in the histological grade of the specimens obtained from TRUSBx and RP, reported by the same pathologist and by the second pathologist were apparent in 6 and 4 cases, and in 7 and 6 patients, respectively. CONCLUSIONS: We recommend that the decision about AS should be made after at least two pathologists have jointly reviewed and agreed on the TRUSBx histology results.