Clear Cell Papillary Renal Cell Carcinoma and XP11.2 Translocation-Associated Renal Cell Carcinoma Are Derived from Distal Nephron Tubules and Proximal-Tubules Respectively.
Ping L Zhang, Mitual B Amin. William Beaumont Hospital, Royal Oak, MI
Background: Clear cell papillary renal cell carcinoma (CCP-RCC) and XP11.2 translocation-associated renal cell carcinoma (XP-TC) are two recently described variants of RCC, but their origin as to which portion of renal tubules they arise from remains unclear. Kidney injury molecule-1 (KIM-1) is a type I transmembranous protein and specific injury marker of proximal tubules. Previous studies have demonstrated that KIM-1 is upregulated in proximal tubule derived RCC (clear cell RCC and papillary RCC) but negative in distal nephron tubule derived tumors (chromophobe RCC and oncocytoma). We attempted to determine the origin of CCP-RCC and XP-TC using KIM-1 expression. Since KIM-1 has a phagocytotic function in injured proximal tubules, we also investigated for correlation with CD68 expression, which is a phagocytic transmembrane glycoprotein, mainly present in macrophages.
Design: The study included three group of RCC. Group 1 had 16 cases which included both clear cell RCC and papillary RCC (KIM-1 positive control group), Group 2 consisted of 11 cases of CCP-RCC (CK7 positive/P504S negative) and Group 3 had 11 cases of XP-TC (TFE-3 positive). Tumors were immunohistochemically stained for KIM-1 (AKG7 monoclonal antibody, JB Bonventre's lab, Brigham and Women's Hospital, Boston) and CD68 (KP1 clone, Dako Cytomation) and staining intensity was graded from 0 to 3+.
Results: KIM-1 showed membranous and/or cytoplasmic staining in all group 1 cases (16/16; 5 with 1+, 7 with 2+ and 4 with 3+ staining). None of group 2, CCP-RCC cases (0/11) expressed KIM-1. In contrast, all group 3, XP-TC cases (11/11) revealed positive KIM-1 expression (1 with 1+, 7 with 2+ and 3 with 3+ staining), suggesting origin from proximal tubules. The cytoplasmic expression of CD68 was present all group 1 cases (16/16, 5 with 1+, 7 with 2+ and 4 with 3+ staining), absent in all group 2 cases (0/11); and present in 9/10 group 3 cases (2 with 1+, 7 with 2+ and 1 with 3+ staining, 1 case was not available).
Conclusions: Using KIM-1 as a differentiation marker, the negative staining in CCP-RCC suggests derivation from distal nephron tubules and positive staining in XP-TC suggests derivation from proximal tubules. CD68 expression closely mirrored KIM-1 expression both in extent and intensity. The expression of CD68 in RCC subtypes is a novel finding and in our opinion this CD68 expression most likely represents a functional relationship with KIM-1, and may not necessarily have a real diagnostic utility; although this finding needs further evaluation.
Category: Genitourinary (including renal tumors)
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 88, Wednesday Morning