Cyclin D1 expression in prostate carcinoma

The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in REPLACE_GT5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≧7), 86% of patients demonstrated cyclin D1 immunostaining of REPLACE_GT5% (PREPLACE_LT0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (PREPLACE_LT0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness.

Cyclin D1 expression in prostate carcinoma.

The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in >5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≥7), 86% of patients demonstrated cyclin D1 immunostaining of >5% (P<0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (P<0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness.

The prognostic value of cyclin D1 in renal cell carcinoma.

INTRODUCTION: Renal cell carcinoma (RCC) is a family of distinct tumors, and a variety of molecules have been evaluated as prognostic markers for RCC. Cyclin D1, a cell cycle regulator, is overexpressed in several primary tumors. OBJECTIVE: To evaluate cyclin D1 expression as a prognostic marker in RCC. METHOD: In total, 109 tumor specimens from patients with RCC were obtained from 2005 to 2010 at Hospital das Clínicas--Ribeirão Preto School of Medicine--USP, Brazil, and submitted to immunohistochemical analysis along with seven normal kidney tissue samples. RESULTS: All of the normal kidney samples lacked cyclin D1 immunohistochemical staining. In addition, there was lower protein expression in the papillary and chromophobe RCC samples. Patients with cyclin D1(low) tumors (≤ 30 % positive cells) showed worse clinical outcome (p = 0.03), lower survival without metastasis and/or death by RCC (p = 0.03), high nuclear grade (p = 0.001), larger tumor size (p = 0.01), presence of symptoms at diagnosis (p = 0.04), necrosis (p = 0.004) and sarcomatoid morphology (p = 0.04). After multivariate analysis, cyclin D1 was not an independent significant factor for worse outcome; however, it improved the accuracy of the adopted prognostic system. The analysis performed for clear cell RCC alone showed similar statistical significance to that of the total cases. CONCLUSIONS: Cyclin D1 protein was overexpressed in RCC. The types of RCC appear to exhibit different immunohistochemical staining patterns for cyclin D1; high protein expression was related to good clinical outcome and to most known favorable prognostic factors. Further investigations are necessary to reveal which mechanisms lead to cyclin D1 accumulation in neoplastic cells.

NF-kB expression in IgA nephropathy outcome.

Some studies have demonstrated the involvement of nuclear factor-kappa B (NF-kB) in the pathogenesis of glomerulonephritis. The aim of our study was twofold: (1) to analyze the prognostic value of NF-kB expression in primary IgA nephropathy (IgAN) and (2) to compare the results of NF-kB expression by immunohistochemistry (IHC) and southwestern histochemistry (SWH). We analyzed 62 patients diagnosed with IgAN from 1987 to 2003. We used monoclonal antibodies to CD68 and mast cell tryptase and polyclonal antibodies to TGF-ß1, α-SMA and NF-kB p65. We used SWH for the in situ detection of activated NF-kB. The results showed that NF-kB expression (mainly by SWH) correlated with clinical and histological parameters. An unfavorable clinical course of IgAN was significantly related to tubular NF-kB expression by SWH, but not by IHC. The Kaplan-Meier curves demonstrated that increased NF-kB expression, which was measured by IHC and SWH, decreased renal survival. In conclusion, the increased expression of NF-kB in the tubular area may be a predictive factor for the poor prognosis of patients with IgAN. Compared with IHC, NF-kB expression determined by SWH was correlated with a larger number of parameters of poor disease outcome.

Renal disorders involved in the pathophysiology of urinary excretion of a-1 microglobulin in patients with glomerulopathies.

AIMS: The protein alpha1-microglobulin (alpha1-microg) is filtered by the glomeruli and fully reabsorbed by the proximal tubules, and tubulointerstitial injury compromises its reabsorption. The aim of this study was to determine which functional, morphological and inflammatory renal disorders associated with tubulointerstitial damage interfere with urinary excretion of alpha1-microg in patients with glomerulopathies. PATIENTS AND METHODS: 38 patients (33.6 +/- 11.3 years) with primary or secondary glomerulopathies diagnosed by renal biopsies were studied. The urinary fractional excretion of alpha1-microg (FEalpha1-microg), the urinary monocyte chemoattractant protein-1/urinary creatinine (UMCP-1) index and 24-h proteinuria were determined. In the cortex of renal biopsies, the number of macrophages/104 microm2 of glomerular tuft (GT) and tubulointerstitial (TI) areas, the relative interstitial area (RCIA), and the relative interstitial fibrosis area (CIF) were measured. Results are reported as median and range and the Spearman non-parametric test was used to determine the correlations. RESULTS: FEalpha1-microg was 0.165% (0.008% - 14,790.0%) in patients with glomerulopathies and 0.065% (0.010% - 0.150%) in the control group (p < 0.05; Mann-Whitney U-Test). FEalpha1-microg was correlated with creatinine clearance (r = -0.4396; p = 0.0358), UMCP-1 index (r = 0.5978; p < 0.0001), number of macrophages/TI area (r = 0.5634; p = 0.0034) and RCIA (r = 0.7436; p < 0.0001). However, FEa1-microg was not correlated with proteinuria (r = 0.1465; p = 0.5153) or with CIF (r = 0.0039; p = 0.98). CONCLUSIONS: renal MCP-1 and the expansion and number of macrophages of the tubulointerstitial area participate in the increase of urinary excretion of alpha1-microg in patients with glomerulopathies. Although proteinuria and interstitial fibrosis have not been associated with this effect, the present study does not exclude some of these disorders in the pathophysiology of urinary excretion of alpha1-microg.

Mast cells, TGF-beta1 and alpha-SMA expression in IgA nephropathy.

IgA nephropathy (IgAN) is a kidney disease with a varying renal prognosis. Recently, many studies have demonstrated that renal alpha-smooth muscle actin (alpha-SMA) and transforming growth factor (TGF-beta1) expression, as well interstitial mast cell infiltrates could represent a prognostic marker in several renal diseases. The aim of our study was to analyze the prognostic value of mast cell, TGF-beta1 and alpha-SMA expression in IgAN. A survey of the medical records and renal biopsy reports of 62 patients with a diagnosis of IgAN followed-up from 1987 to 2003 was performed. The mean follow-up time was 74.7 +/- 50.0 months. The immunohistochemical studies were performed using a monoclonal antibody anti-human mast cell tryptase, a polyclonal antibody anti-human TGF-beta1, and a monoclonal antibody anti-human alpha-SMA. An unfavorable clinical course of IgAN was related to interstitial mast cell infiltrates and alpha-SMA expression in the tubulointerstitial area. Expression of glomerular TGF-beta1 and alpha-SMA, and interstitial TGF-beta1 is not correlated with clinical course in IgAN. In conclusion, the increased number of mast cells and higher alpha-SMA expression in the tubulointerstitial area may be predictive factors for the poor prognosis of patients with IgAN.

Alpha-SM actin expression as prognostic indicator in IgA nephropathy (Berger's disease).

Recent studies have demonstrated that alpha-Smooth Muscle actin expression in glomerular and tubulointerstitial compartments of renal tissue could represent a prognostic marker in several renal diseases. Our objective was to identify the prognostic value of alpha-SM actin actin expression on the evolution of renal damage in Primary IgA nephropathy (Berger's disease). 43 patients followed up from 1988 to 1999 at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of Sao Paulo, Brazil, was studied. Clinical-laboratory data were obtained from the medical records of the patients using a protocol containing name, race, gender, origin, profession, age at clinical presentation of the disease and personal and family history. The parameters assessed in the approach to IgA nephropathy were serum creatinine, creatinine clearance, serum albumin, total serum protein, 24 hours proteinuria, glycaemia, serum sodium, potassium, calcium and phosphorus ions, analysis of urinary sediment, serum complement profile, blood count, and renal biopsy. Morphological evaluation was performed by renal biopsy using common light and immunofluorescence microscopy. Immunohistochemical studies were performed using a murine monoclonal antibody to alpha-SM actin. Our data showed that alpha-SM actin expression in the glomerular and tubulointerstitial compartments are not correlated with unfavorable clinical course of primary IgA nephropathy.