Expression of epithelial-mesenchymal transition markers in renal cell carcinoma: impact on prognostic outcomes in patients undergoing radical nephrectomy.
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.


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 patients positive for one or two risk factors (31.5%) and 14 of 23 patients positive for three or four risk factors (60.9%).


CONCLUSIONS
• 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.
Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
Ken-ichi
K
Harada
Hideaki
H
Miyake
Yuji
Y
Kusuda
Masato
M
Fujisawa
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan / Q000453:epidemiology; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality; D009392:Nephrectomy; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends
D014408:Biomarkers, Tumor