Refining Fuhrman Nuclear Grading for Clear Cell Renal Cell Carcinoma
H Aydin, P Elson, L Sercia, R Baehner, B Rini, M Zhou. Cleveland Clinic, Celeveland; Genomic Health Institution, Redwood
Background: The Fuhrman nuclear grading (FNG) system that utilizes nuclear size, shape and nucleolar prominence is the most widely used grading system for clear cell renal cell carcinoma (CCRCC) due to its well established prognostic significance. However, CCRCCs are heterogeneous and may have more than one grade within the same tumor. It is not clear how this grade heterogeneity impacts tumor behavior. Using FNG criteria, we explored if incorporation of grade heterogeneity may provide better clinical prognostication in comparison to the standard FNG.
Design: 584 cases of clinically localized RCC were reviewed and graded using the standard FNG system. In addition, the highest grade and its estimated percentage as well as the predominant (quantitatively dominating) grade were recorded. The results were then correlated with recurrence free survival (RFS) and overall survival (OS).
Results: All but 1 case (99.8%) had 3 different grades within the same tumor. Using standard FNG analysis, grade 1/2, 3 and 4 was seen in 65%, 26% and 9% cases respectively. In the highest grade analysis, grade 2, 3 and 4 was seen in 60%, 28% and 12% cases and by predominant grade analysis, grade 1, 2, 3/4 was seen in 20%, 70% and 10% cases. All the three analyses (standard FNG, highest grade, predominant grade) highly correlated with each other. The results of highest and standard FNG analyses were concordant in 93% of cases (541/584) and differed by 1 grade in minority (43) (7%) of the cases. All three analyses were significantly associated with both RFS and OS. Prognostically, the predominant grade was the best fit to RFS and standard FNG was the best fit to OS. A recursive partitioning algorithm demonstrated that for the highest grade analysis, presence of 60% or greater grade 2 component and 10 % or greater grade 4 component respectively, could further separate grade 2 and 4 tumors into prognostically different subgroups.
Conclusions: Both the standard FNG system and incorporating the highest and predominant grades for grade heterogeneity significantly correlate with the clinical outcomes. However, our quantification of grade 2 and 4 components combined with the highest grade seems to provide additional prognostic value.
Category: Genitourinary (including renal tumors)
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 165, Tuesday Morning