Clin Invest Med 2008; 31 (1): E8-E15. AbstractObjective: Ki-67 is a proliferation-associated nuclear antigen and is expressed in all cycling cells except for resting cells in the G0-phase. PCNA is an acidic nuclear protein and has been recognized as a histologic marker for the G1/ S phase in the cell cycle. Ki-67and PCNA labeling indices are considered to reflect cell proliferation, particularly, growth fraction. The purpose of this study is to investigate the expression levels of Ki-67 and PCNA in prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and their potential on the early diagnosis of PCa. Methods: Human prostate cancer cell lines LNCaP and PC-3, human normal prostate epithelial cell line HuPEC, tissues from patients with PCa (121 cases) and BPH (45) and 36 normal cases were examined for the expression of Ki-67 and PCNA by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Then, the association of Ki-67 and PCNA expression with clinical grading of PCa was analyzed by immunohistochemistry staining. Results: The ratios of PCNA and Ki-67 expression levels in LNCaP and PC-3 were higher (P<0.05, P<0.001) than that in HuPEC. The two markers were differentially expressed in three tissues and showed increased expression in PCa (P<0.05) and BPH (P<0.05), relative to human normal prostate tissues. Compared with BPH, the ratio of Ki-67 and PCNA expressed in tumour tissue was increased (P<0.05). The increase of Ki-67 was greater than that of PCNA. Expression of the two markers increased after different grading of PCa cases Prostate cancer (PCa) is the second most frequent cause of male cancer-related death in the United States of America (USA) and Western Europe. Its incidence is continuously rising, with over 200 000 new cancers and 35 000~40 000 deaths per year, 1 Carcinogenesis and the mechanisms influencing the progression and prognosis of PCa is a multistep process, involving both genetic insults to epithelial cells and changes in epithelial-stromal interactions. 2 Despite extensive research PCa is not understood.There are two proliferative markers-Ki-67 and proliferating cell nuclear antigen (PCNA). Ki-67 antigen is expressed in proliferative cells throughout the G1, S, G2, and M phases, and provides a reliable index of cellular proliferation 3,4 PCNA is an acidic nuclear protein, expressed mainly in phase S of the cellular cycle. It becomes active, in various tissues par-

Aim: CD147 and MMPs have been demonstrated to be involved in tumor invasion and angiogenesis. The aim of this study was to analyze the clinicopathological significance of CD147, MMP-1, MMP-2 and MMP-9 expression in human prostate cancer (PCa) and to evaluate their involvement in the progression of PCa. Methods: CD147, MMP-1, MMP-2 and MMP-9 expression was assessed in paraffin-embedded specimens collected from 62 cases of PCa and 15 cases of benign prostatic hyperplasia (BPH) by immunohistochemistry. Spearman’s correlation was applied to determine possible relationships between CD147, MMP-1, MMP-2 and MMP-9 expression and PCa. The association of CD147 and MMP-2 protein expression with the clinicopathological characteristics and the prognosis of PCa was subsequently assessed. Results: CD147was expressed in 51/62 (82.3%) PCa patients and in 2/15 (13.3%) BPH cases. MMP-1, MMP-2 and MMP-9 expression was significantly higher in PCa tissue than in BPH tissue. Using Spearman analysis, a significant positive correlation between CD147 and MMP-1, MMP-2 and MMP-9 expression was found (p <0.05). CD147 and MMP-2 expression was correlated with TMN grade and Gleason score. Patients with concurrent expression of CD147+ and MMP-2+ had the lowest survival (p <0.01). Conclusion: The results suggest that concurrent expression of CD147 and MMP may be an important characteristic of PCa which may help in the prediction of PCa progression.

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The expression of CD147 or VEGF may be an important feature of advanced RCC. A combined detection of CD147/VEGF coexpression may benefit us in the prediction of the prognosis of advanced RCC.

The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous-sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs,), increased frequency of nonsynonymous SSNVs in PanCancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel-Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD2), phosphatase and tensin homolog (PTEN). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 (TP53) mutations in 32% of tumors (P = 5.47 × 10 −17 ); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers ATrich interaction domain 1A (ARID1A) and BRCA1 associated protein 1 (BAP1) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers.

Although several studies have assessed the association between total fluid intake, specific drinks and bladder cancer, no firm conclusions can yet be drawn. Four hundred thirty two bladder cancer cases and 392 frequency matched hospital-based controls recruited in the South and East of China between October 2005 and June 2008 were interviewed on their intake of 6 nonalcoholic and 3 alcoholic drinks. Age, sex, smoking and hospital-adjusted odds ratios (OR) and 95 percent confidence intervals (95% CI) were calculated for all drinks and for total fluid intake using logistic regression. For 381 cases (81.9% men) and 371 controls (76.3% men), total fluid intake could be calculated. In men, an increase in total fluid intake was associated with a significantly decreased bladder cancer risk (OR 0.93, 95% CI: 0.88-0.99, per cup fluid consumed). Neither green nor black tea consumption was associated with bladder cancer. Daily consumption of milk significantly reduced the risk of bladder cancer by a half (OR 0.49, 95% CI: 0.32-0.76), which strengthens earlier suggestions that milk is probably associated with a decreased bladder cancer risk. Consumption of wine (OR 0.49, 95% CI: 0.34-0.70) and liquor/spirits (OR 0.65, 95% CI: 0.47-0.92) were associated with a significantly reduced risk. Consumption of water, fruit juice and beer appeared not associated with bladder cancer. There is no clear indication that the risks observed in this Chinese population are substantially different from those observed in Caucasian populations.

Background and Aim. CC chemokine ligand 18 (CCL18) promotes malignant behaviors of various human cancer types. However, its involvement in human prostate cancer has not been fully elucidated. The aim of this study was to investigate the role of CCL18 in PCa. Methods. Expression of CCL18 at mRNA and protein levels was detected using real-time qRT-PCR and immunohistochemistry analysis. We analyzed the associations of CCL18 expression with clinical features of human PCa. The effects of PCa cell migration, invasion, and apoptosis were tested. The efficiency of CCL18 on prostate tumor growth was assessed in a subcutaneous xenograft model. Results. CCL18 expression was upregulated (both P < 0.01) in PCa tissues compared with those in noncancerous prostate tissues. CCL18 upregulation was correlated with high Gleason score (P = 0.034) of patients with PCa. rCCL18 stimulation in PCa cells promoted cell migration and invasion but decreased DU145 cells apoptosis rate. Furthermore, subcutaneous homografts models showed the increased tumor growth and tumor vascularization with the CCL18 stimulation, and the expression of Ki67, PCNA, and CD31 in CCL18 stimulation mice was also significantly increased. Conclusions. Our data offer the convincing evidence that the upregulation of CCL18 may be involved in the malignant progression of PCa.