What's known on the subject? and What does the study add? There have been few studies evaluating the prognostic value of epithelial‐mesenchymal transition markers in renal cell carcinoma (RCC); therefore, the significance of these markers in the prognosis of patients with RCC, particularly that in those with localized disease, remains largely unknown. Consideration of the expression levels of potential epithelial‐mesenchymal transition markers, particularly clusterin and Twist in addition to conventional prognostic parameters, would contribute to the prediction of disease recurrence after radical nephrectomy for localized renal cell carcinoma. OBJECTIVE: To evaluate the expression of multiple molecular markers involved in the process of epithelial–mesenchymal transition (EMT) in renal cell carcinoma (RCC) with the aim of clarifying the prognostic significance of these markers in patients undergoing radical nephrectomy. PATIENTS AND METHODS: The expression levels of 11 EMT markers, including E‐cadherin, N‐cadherin, β‐catenin, γ‐catenin, clusterin, Slug, Snail, Twist, vimentin, ZEB1 and ZEB2, in radical nephrectomy specimens from 122 patients with clinically localized RCC were measured by immunohistochemical staining. RESULTS: In this series, disease recurrence occurred in 39 (32.0%) patients, with a 5‐year recurrence‐free survival rate of 64.4%. Univariate analysis identified expression levels of E‐cadherin, clusterin, Twist and vimentin, in addition to C‐reactive protein (CRP) level, pathological stage and microvascular invasion, as significant predictors for disease recurrence. Of these, expression levels of clusterin and Twist, CRP levels and microvascular invasion appeared to be independently related to disease recurrence on multivariate analysis. There were significant differences in recurrence‐free survival according to positive numbers of these four independent factors: disease recurrence occurred in two of 26 patients negative for any risk factor (7.7%), 23 of 73 pateints positive for one or two risk factors (31.5%) and 14 of 23 patients positive for three or four risk factors (60.9%). CONCLUSION: Consideration of the expression levels of potential EMT markers, particularly clusterin and Twist, in RCC specimens, in addition to conventional prognostic parameters, contributes to the accurate prediction of disease recurrence after radical nephrectomy for localized RCC.

Background/Aim: It is important to delay the emergence of castration-resistant phenotype to improve the prognosis in patients with metastatic castration-sensitive prostate cancer (mCSPC). The objective of this study was to investigate the prognostic impact of time to castration resistance (TTCR) in mCSPC patients. Patients and Methods: This study included 437 consecutive mCSPC patients whose primary androgen deprivation therapy was judged to have failed. Prognostic outcomes in these patients were investigated by dividing them into the following 4 groups of 82, 104, 133 and 118 patients with TTCR 0-6, 6.1-12, 12.1-18 and ≥18.1 months, respectively. Results: The mean value of TTCR in the 437 patients was 18.7 months. Of several baseline parameters, significant differences among the 4 groups were noted in the performance status, prostate-specific antigen (PSA) level, lactate dehydrogenase (LDH) level, alkaline phosphatase (ALP) level and Gleason score, all of which favored longer TTCR groups. Furthermore, despite the lack of a significant difference in time from the development of castration-resistant disease to death among the 4 groups, there was a significant difference in overall survival (OS) from diagnosis among these groups, showing prolonged OS proportional to TTCR. Univariate analysis identified the age, PSA level, LDH level, ALP level, Gleason score, visceral metastasis and TTCR as significant predictors of OS, of which only age, ALP level and TTCR were shown to be independently associated with OS on multivariate analysis. Conclusion: mCSPC patients with a longer TTCR are likely to achieve a more favorable OS.

OBJECTIVES: To evaluate the significance of clusterin expression in surgically resected renal cell carcinoma (RCC) specimens. PATIENTS AND METHODS: Normal kidney and RCC specimens were obtained from 131 patients who had radical surgery. The expression of clusterin protein was analysed by immunohistochemical staining with an antibody recognizing all isoforms of clusterin. Cell proliferative activities and apoptotic features in these specimens were investigated using Ki‐67 immunostaining and the terminal deoxynucleotidyl transferase mediated dUTP nick‐end labelling assay, respectively. Findings were evaluated in relation to several clinicopathological factors. RESULTS: There were various levels of clusterin expression in 128 of the 131 RCC specimens, while 37 of 131 normal kidney tissues (28.2%) had no clusterin staining. Clusterin protein was present in the cytoplasm of both normal and cancer cells, but there was no nuclear staining identified in either type of cell. The expression level of clusterin protein in RCC tissues was significantly related to tumour stage and grade, but not to age, gender or histological cell type. Cell proliferative activity in RCC specimens was significantly associated with clusterin expression, while the apoptotic index was inversely related to clusterin expression. Furthermore, recurrence‐free survival in patients with strong clusterin expression was significantly lower than that in those with weak expression. CONCLUSIONS: These findings suggest that the secreted form of clusterin may be involved in the progression of RCC, and that overexpression of clusterin could be a useful prognostic variable after radical surgery in patients with RCC.

What's known on the subject? and What does the study add?: There have been few studies evaluating the prognostic value of epithelial–mesenchymal transition markers in prostate cancer; therefore the significance of these markers in the prognosis of patients with prostate cancer, particularly those with localized disease, remains largely unknown. Consideration of the expression levels of potential epithelial–mesenchymal transition markers, particularly Twist and vimentin, in addition to conventional prognostic parameters would contribute to the prediction of biochemical recurrence after radical prostatectomy for localized prostate cancer. Objective: To analyse the expression patterns of multiple molecular markers implicated in epithelial–mesenchymal transition ( EMT ) in localized prostate cancer ( PC ), in order to clarify the significance of these markers in patients undergoing radical prostatectomy ( RP ). Patients and Methods: Expression levels of 13 EMT markers, namely E‐cadherin, N ‐cadherin, β‐catenin, γ‐catenin, fibronectin, matrix metalloproteinase ( MMP ) 2, MMP ‐9, Slug, Snail, Twist, vimentin, ZEB 1 and ZEB 2, in RP specimens from 197 consecutive patients with localized PC were evaluated by immunohistochemical staining. Results: Of the 13 markers, expression levels of E‐cadherin, Snail, Twist and vimentin were closely associated with several conventional prognostic factors. Univariate analysis identified these four EMT markers as significant predictors for biochemical recurrence ( BR ), while serum prostate‐specific antigen, Gleason score, seminal vesicle invasion ( SVI ), surgical margin status ( SMS ) and tumour volume were also significant. Of these significant factors, expression levels of Twist and vimentin, SVI and SMS appeared to be independently related to BR on multivariate analysis. There were significant differences in BR ‐free survival according to positive numbers of these four independent factors. That is, BR occurred in four of 90 patients who were negative for risk factors (4.4%), 21 of 83 positive for one or two risk factors (25.3%) and 19 of 24 positive for three or four risk factors (79.2%). Conclusion: Measurement of expression levels of potential EMT markers, particularly Twist and vimentin, in RP specimens, in addition to conventional prognostic parameters, would contribute to the accurate prediction of the biochemical outcome in patients with localized PC following RP .