[1006] An Analysis of INI1 Nuclear Expression in Collecting Duct Carcinoma (CDC) and Renal Medullary Carcinoma (RMC): Diagnostic and Pathogenetic Implications

M Vankalakunti, AM Gown, R Gupta, RB Shah, RS Parakh, DE Westfall, M Amin, DJ Luthringer, LC Goldstein, MB Amin. Cedars-Sinai Medical Center, Los Angeles, CA; PhenoPath Laboratories, Seattle, WA; William Beaumont Hospital, Royal Oak, MI; University of Michigan, Michigan, MI

Background: INI1/hSNF5 is a component of tumor suppressor gene complex, mutations of which lead to inactivation of the gene contributing to tumorigenesis. It has been described in RMC, a distinctive tumor occuring exclusively in patients with sickle cell trait and which shares many features with CDC. Some experts believe that RMC is a subtype of CDC based on marked overlap in clinical, gross and microscopic features. There is also overlap in reported immunohistochemical (IHC) expression. We further explore the interrelationship between these extremely rare renal tumors, CDC and RMC, based on INI-1 expression.
Design: Five cases of CDC and four cases of RMC were immunostained using anti-INI1 antibody (clone 25/BAF47; 1:200; BD Biosciences, CA). All RMC cases were in African Americans, three with electrophoresis and/or clinical history supporting sickle cell trait and one with morphology (reticular, yolk sac tumor-like appearance) supporting RMC. CDC cases had diagnostic features including mass with epicenter in renal medulla, high grade infiltrative tubulopapillary appearance with associated desmoplasia and absence of urothelial carcinoma of the renal pelvis or primary elsewhere.
Results: Clinicopathologic analysis showed overlap between CDC and RMC: mean age (CDC-44 y, RMC-43.75 y); morphology (infiltrative tubulopapillary architecture with associated desmoplasia); IHC (UEA-1, CK7 and HMWCK positive); and clinical outcome (CDC and RMC, death due to disease). In addition to overlap with CDC, two cases of RMC showed a reticular yolk sac tumor-like histology. Nuclear immunoreactivity for INI1 was noted in all normal renal parenchymal (epithelial and stromal) and inflammatory cells. This protein expression correlates with molecular absence of INI1 mutation in normal tissue. All CDC cases showed diffuse, strong positivity in tumoral and non-epithelial tissue. All cases of RMC showed loss of INI1 expression.
Conclusions: 1) Marked overlap in clinicopathologic characteristics between RMC and CDC suggests close interrelationship. 2) Loss of INI1 protein expression is a consistent observation in RMC suggesting a causative role in this tumor occurring in sickle cell patients. 3) The discriminatory IHC between RMC and CDC suggests diagnostic utility.
Category: Genitourinary (including renal tumors)

Tuesday, March 23, 2010 9:30 AM

Poster Session III # 145, Tuesday Morning


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