Outcome prediction for renal cell carcinoma: evaluation of prognostic factors for tumours divided according to histological subtype

A wide variety of parameters have been investigated for their prognostic significance in mixed series of renal cell carcinoma (RCC). The classification of RCC into separate types with differing morphology, genotype and probable clinical outcome has led to a re-evaluation of many prognostic parameters with studies confined to a single RCC morphotype. Tumour stage remains the most important predictor of RCC outcome and recent investigations have focused upon tumour diameter and the prognostic significance of stromal, vascular and lymphatic invasion within the renal sinus. In large tumour series, morphotype has been correlated with patient survival, with clear cell RCC being associated with a less favourable outcome than chromophobe RCC and to a lesser extent papillary RCC, for organ confined tumours. The prognostic significance of nuclear grading remains controversial. Fuhrman grading has been shown to have prognostic utility for clear cell RCC in some series. Recent studies have shown that for papillary RCC, grading should be based upon nucleolar size and that Fuhrman grading is inappropriate for chromophobe RCC. Proliferative indices based upon a variety of markers have been correlated with outcome for clear cell RCC (Ki-67, AgNORs, p21(waf1/cip1) and p27(Kip1)) and papillary RCC (Ki-67, AgNORs), although in some series prognostic significance was lost on multivariate analysis. The presence of tumour necrosis has been shown to predict survival for clear cell and chromophobe RCC, and in clear cell RCC quantification of tumour vascular density has been correlated with outcome. Several molecular markers have been investigated for prognostic significance, mostly in clear cell RCC. Although some of these markers have been shown to be significantly associated with survival, these findings remain to be confirmed in large scale follow-up studies.