Immunohistochemical Loss of INI-1 Expression in Collecting Duct Carcinomas (CDC)
H Elwood, L Schultz, PB Illei, DE Baydar, A Billis, JE Epstein, GJ Netto. Johns Hopkins University, Baltimore; UNICAMP State University, Campinas, Sao Paulo, Brazil; Hacettepe, Ankara, Turkey
Background: CDC is a rare and aggressive renal tumor with a tendency to involve renal sinus. CDC displays variable morphologic features that may overlap with those of renal medullary carcinoma (RMC). Loss of INI-1 tumor suppressor gene was initially demonstrated in pediatric malignant rhabdoid tumor of kidney. Recently, LOH of hSNF5/INI gene and loss of INI-1 immunoexpression was demonstrated in RMC. The current immunohistochemical study assesses INI-1 expression in a series of CDC.
Design: 20 archival cases of CDC (1990-2009) from the three participating institutions were used to construct a tissue microarray (TMA). Each tumor was spotted 3-7 times. Immuno-expression of INI-1 was evaluated using a standard immunohistochemistry protocol and appropriate controls. Percentage of positive nuclear staining was categorized as focal (<25%), multifocal (25-75%) or diffuse (>75%). Intensity of staining (0 to 3+) was also noted for each tumor. An H-score was calculated for each CDC as the product of intensity x extent and was later correlated with clinico-pathological parameters and outcome data.
Results: In our cohort, mean age was 61 years, M:F ratio was 2.4 . The mean length of follow-up was 32 months (2-151). Disease progression and disease specific survival (DSS) rates were 34% and 64%, respectively. Complete loss of INI-1 expression was observed in 4/20 (20%) cases of CDC. Two additional cases revealed only focal (<25%) and weak intensity (1+) staining. The remaining tumors showed multifocal or diffuse INI-1 expression with variable intensity of staining (1 to 3+). We found no significant correlation between Loss of INI-1 and patient demographics, maximum tumor dimension, nuclear atypia or presence of sarcomatoid features (p:NS). Loss of INI-1 in CDC did not predict disease progression or DSS in our cohort of cases (p:NS).
Conclusions: This is the first study to show loss of expression of INI-1 tumor suppressor gene in CDC. Almost one third (30%) of our CDC tumors showed complete loss or only minimal (focal and weak) immunoexpression of INI-1 . The current findings identifies yet one more overlapping feature between RMC and CDC. Additional molecular confirmation of INI-1 gene loss in our CDC cases will be pursued.
Category: Genitourinary (including renal tumors)
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 120, Monday Morning