The highest Fuhrman and WHO/ISUP grade influences the Ki-67 labeling index of those of grades 1 and 2 in clear cell renal cell carcinoma

Abstract

Nuclear grade is one of the most important prognostic factors in clear cell renal cell carcinoma (CCRCC). Although CCRCCs usually have intratumoral heterogeneity with various nuclear atypia including nucleolar prominence, it is unclear whether a similar degree of nuclear grade component demonstrates the same proliferative activity. We aimed to reveal whether the presence of a higher nuclear grade has an effect on proliferative activity among each assigned nuclear grade in CCRCCs. We enrolled 129 CCRCC patients containing at least two different nuclear grades. We separately assessed nuclear grade using the Fuhrman and World Health Organization and International Society of Urologic Pathologists (WHO/ISUP) grading systems. In addition, we selected blocks containing different nuclear grade and assessed the Ki-67 labeling index (LI) for each using a computer-based analysis system. Ki-67 LIs significantly correlated with both Fuhrman and WHO/ISUP grades (P < 0.001 and P < 0.001). Of note, the LIs among Fuhrman and WHO/ISUP grades 1 and 2 were also statistically significant according to the highest nuclear grade (P < 0.01 for both grades 1 and 2). Our data suggests that the highest nuclear grade influences the proliferative activity in tumor components regardless of the morphologically assigned nuclear grades. The exact evaluation of Ki-67 LI in CCRCC can provide a more precise information of the malignant potential.

Keywords: Fuhrman nuclear grading; Ki-67 labeling index; WHO/ISUP nuclear grading; clear cell renal cell carcinoma; intratumoral heterogeneity.