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Chair of Urology Endourology, Oncologic Urology Unit “Federico II” University, Napoli

Multidrug-resistance protein (MDR-1) and other predictors of prognosis in renal cell carcinoma V. Altieri. Chair of Urology Endourology, Oncologic Urology Unit “Federico II” University, Napoli. Roma, november 7th, 2008. INTRODUCTION 1. MORE EFFECTIVE DRUGS GREATER SCIENTIFIC INTEREST

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Chair of Urology Endourology, Oncologic Urology Unit “Federico II” University, Napoli

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  1. Multidrug-resistance protein (MDR-1) and other predictors of prognosis in renal cell carcinoma V. Altieri Chair of Urology Endourology, Oncologic Urology Unit “Federico II” University, Napoli Roma, november 7th, 2008

  2. INTRODUCTION 1 MORE EFFECTIVE DRUGS GREATER SCIENTIFIC INTEREST NEED FOR BETTER ASSESSMENT OF THE CLINICAL FEATURES BETTER “PROGNOSTIC ASSESSMENT”

  3. INTRODUCTION 2 • Tumor size • T stage • Metastasis (nodal and visceral and/or skeletal) • Grade (Fuhrman) • ECOG PS • Symptoms at presentation • Histology type • Prognostic Biomarkers • Sex • Age

  4. T LOCAL INVASION T VENOUS INVASION Renal sinus Perinephric fat Gerota’s fascia Adrenal Renal Caval (Infiltration ?) Atrial

  5. T STAGE

  6. TNM (2002) V = neoplastic thrombus involvement V0 – absent V1 – renal vein V2 – caval (infradiaphragmatic) V3 – caval (supradiaphragmatic)

  7. T – PROGNOSTIC VALUE Ficarra V et al; Urol 2004 * Tsui K; J. Urol 2000

  8. PROPOSAL FOR A NEW STAGING CLASSIFICATION Ficarra V; J. Urol 2007 (p < 0,0001)

  9. T – STAGE:PROGNOSIS Ficarra V; J. Urol 2007 (p < 0,0001)

  10. TNM STAGE GROUPING

  11. “STAGE GROUPING” PROGNOSTIC VALUE Tsui K; J. Urol 2000 (p < 0,001)

  12. GRADING (FUHRMAN) Tumor Stage (p=0.0001) Synchronous metastases (p=0.003) Lymphnode involvment (p=0.0001) Renal vein involvment (p=0.0001) Tumor size (p=0.0001) Perirenal fat involvement (p=0.001) Multicentricity (p=0.14) correlation Nuclear grade Bretheau D, et al Cancer 1995 dec 15;76(12):2543-9

  13. RENAL CARCINOMAHISTOLOGY Amin, M.B. et al; Am. Jour Surg Pat 2002 Karakiewicz P.I. et al; BJU International 2007 Moch et al; Cancer 2000 Patard JJ et al; J Clin Oncol 2005

  14. HISTOLOGICAL FEATURES PROGNOSIS

  15. SYMPTOMS AT DIAGNOSIS ECOG PS Tumor size (cm) T stage Fuhrman G Renal vein invasion N+ adrenal extension M+ Correlated with P = 0,001 Age Sex Histology Not significant Not correlated with Patard JJ et al; Eur Urol 2003

  16. SYMPTOMS AT PRESENTATIONPROGNOSIS

  17. DIAGNOSTIC AND PROGNOSTIC MOLECULAR MARKERS IN RENAL CELL CARCINOMA Hari S. G. R. Tunuguntla et Merce Jorda; J Urol 2008

  18. MULTIDRUG RESISTANCE Transporter Associated protein MDR-1/P glycoprotein MRP

  19. MDRMETHODS • Paraffin embedded RCC samples • Immunohistochemical technique (Two independent pathologists) Assessment of positivity of the anti-MDR-1 polyclonal primary antibody • Cox multivariate regression analysis • Kaplan-Meyer

  20. MDR-1 IMMUNOHISTOCHEMISTRY The MDR-1 expression in RCC A: low expression of MDR-1 (x100). B: low expression of MDR-1 (x250). C: high expression of MDR-1 (x400). D: high expression of MDR-1 (x400).

  21. MDRMATERIALS

  22. KAPLAN-MEYER

  23. MDRDISCUSSION - CONCLUSIONS • Good correlation with clinical parameters • Parameter of biologic invasiveness ? • Good prognostic significance, also as univariate parameter • Future, possible diagnostic (therapeutic) implications ? • Not very expensive

  24. “TAKE HOME MESSAGE” 1 • Current TNM recommended for prognosis and therapy • T category (T3!) should be refined • T1a • Adrenal invasion ↓ • N category: N2 > N1(?)

  25. “TAKE HOME MESSAGE” 2 • Performance status (ECOG) • Symptoms at presentation GOOD PROGNOSTIC CORRELATION

  26. “TAKE HOME MESSAGE” 3 • Fuhrman grade • RCC subtypes • No biomarker should be routinely used SHOULD BE USED

  27. “TAKE HOME MESSAGE” 4 • Integrated prognostic systems or NOMOGRAMS not routinely recommended in clinical practice, but in stratified inclusion for trials (RISK GROUPS)

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