FACTORES PRONÓSTICOS DEL CARCINOMA DE CÉLULAS RENALES F. Algaba Unidad de Patología Universitat Autònoma de Barcelona

CLASIFICACIÓN CÁNCER RENAL OMS 2016 DE CÉLULAS CLARAS 68.8% PAPILAR 20% CROMÓFOBO 7.3% DE DUCTOS COLECTORES (BELLINI) MEDULAR DE TRANSLOCACIÓN MUCINOSO TUBULAR Y FUSOCELULAR INCLASIFICABLE ACTUALIZACIÓN EN MARCADORES PRONÓSTICOS CLÁSICOS 5.9%

Fuhrman grading Nulear size Nuclear form Nucleoli Grade 1 10  Regular absent Grade 2 15  Irregular 400X Grade 3 20  100x Grade 4 ≥ 20  Bizarre Low mag.

400x 1 2 3 4 Am J Surg Pathol 2011;35:1134–1139

400x 1 2 3 4 Am J Surg Pathol 2011;35:1134–1139

ISUP (nucleolar) Novel Under study

Gelp et al. Am. J. Surg. Pathol.1993; 17: 275 LOW GRADE HIGH GRADE Organ confined RCC shorter survival Grade III and IV versus Grade I and II (p = 0.018). Gelp et al. Am. J. Surg. Pathol.1993; 17: 275

Different pT3a

Sinus invasion

Site fat tissue invasion 5y survival LN Met Met Perinephric 50.9% 7% 28% Sinus. 25.9% 19% 30% J. Urol 2005; 174: 1218-1221 AJSP 2004; 28: 1594-1600

10-year Cancer Specific Survival Microvascular invasion Dall´Oglio BJI. 2007; 100: 552 10-year Cancer Specific Survival MVI (+) 85.1% MVI (-) 96.5% Shindo et al BJI. 2013; Jan 25.

Different pT3a (wall invasion) Mobile thrombus Different pT3a (wall invasion) Wall invasion No wall invasion

Invading tumor thrombus Mobile thrombus Wall invasion 5y overal survival Mobile tumor thrombus 69% Invading tumor thrombus 26% Cases with complete removal 57% Hatcher et al J. Urol. 1991; 145: 20

Median OS Actuarial 5 ys OS Solid thrombus Friable thrombus 44 months 41% Friable thrombus 8 months 15% Bertini et al. Eur. Urol. 2011; 60: 358

pT3b pT3c Cancer Specific Progression free Survival Survival Without peripheral or sinus fat invasion 47% 45% With peripheral & sinus fat invasion 25% 10% Roos et al BJI. 2009 ;104:461

CLASIFICACIÓN CÁNCER RENAL OMS 2016 DE CÉLULAS CLARAS 68.8% PAPILAR 20% CROMÓFOBO 7.3% DE DUCTOS COLECTORES (BELLINI) MEDULAR DE TRANSLOCACIÓN MUCINOSO TUBULAR Y FUSOCELULAR INCLASIFICABLE POSIBLES NUEVOS MARCADORES PRONÓSTICOS 5.9%

CAIX Ki67

CAIX under-expression At median follow-up of 63 months (IQR 35.0– 91.8), on multivariate analysis cutoff points for CAIX 30% cutoff vimentin 50 % CAIX under-expression Vimentin over-expression were associated with worse survival (recurrence, specific and overall survival).

CARCINOMA RENAL DE CÉLULAS CLARAS ENDOTHELIAL CELL CAIX HIF-2α HIF-α VEGF VEGF CAIX Hypoxia inducible factor HIF-2α HIF-α HIF-1α HIF-2α VEGF VEGF HIF-1α HIF-α pVHL 19-30 HIF-2α HIF-α HIF-1α VEGF c-Myc HIF-1α HIF-1  HIF-2α VHL 3p HIF-1  Proliferation Apoptosis Perivascular cell

Proliferación HIF1α HIF2α pVHL normal HIF-1α HIF-2α negativos 12% Nivel de c-Myc similar pVHL deficiente HIF-1α HIF-2α positivos 61% pVHL deficiente Sólo HIF 2α positivo 27% c-Myc Proliferación Gordan et al. Cancer Cell, 2008, 14: 435-446

Después de Sunitinib 83 pacientes con metástasis 10 Hospitales

Después de Sunitinib 83 pacientes con metástasis 10 Hospitales

INMUN