The Study of Xp11 Translocation Renal Cell Carcinoma (RCC) in Adults by TMA, IHC and FISH
M Zhong, L Osborne, MJ Merino, M Hameed, S Aisner. University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark; National Cancer Institute, Bethesda; Memorial Sloan-Kettering Cancer Center, New York
Background: Xp11 translocation renal cell carcinomas (RCC), a distinctive entity in the 2004 WHO renal tumor classification, are rare neoplasms and are often encountered in the pediatric and young adult population. The incidence is probably underestimated partly due to unavailable genetic studies and overlapping histopathological morphology with clear cell and papillary RCC. TFE3 immunohistochemical assay has been used for the diagnosis of the Xp11.2 translocation RCC. However, for a definitive diagnosis, one has to rely on identifying the translocation by genetic and molecular studies.
Design: A total of 120 consecutive adult (>18Y) RCC patient specimens (FFPE during the period 2001-2008) from our institute, were collected to construct a tissue micro array(TMA). IHC was performed on TMA using TFE3 antibody. The 2nd TMA was constructed from all the TFE3 positive specimens, 5 TFE3 negative and 5 TFE3 weak positive specimens. A dual-color, break-apart FISH assay, which can detect the gene rearrangement at Xp11 region, was applied to the 2nd TMA.
Results: Among the 120 RCC, 11(9.2%) cases were TFE3 positive . Among these 11 cases, FISH assay showed split signal, which confirmed chromosome translocations involving TFE3, in 5(4.2%) cases; fusion signal in 1 case; non-conclusive result in the rest 5 cases(most likely due to the ages of the blocks); no split signal in all tested TFE3 negative and weak positive cases. Further more, no TFE3 fusion transcripts (ASPL, PRCC, CLTC, PSF and Nono), but TFE3 wide type were detected by RT-PCR in the tested case with weak TFE3 nuclear stain.
Conclusions: 1) Xp11.2 translocation RCC is not an uncommon neoplasm. The incidence in this group of 120 RCC patients is at least 4.2% in adults (confirmed by FISH). 2) TFE3 IHC is a relatively sensitive and specific assay for the diagnosis Xp11.2 translocation RCC. The strong nuclear TFE3 stain is most likely indicative of Xp11.2 translocation. The weaker nuclear stain appears to be due to expression of full length TFE3 protein, rather than chimeric fusion protein due to translocation. 3) FISH assay is the most reliable method to detect Xp11 translocation RCC, when only FFPE material is available.
Category: Genitourinary (including renal tumors)
Monday, March 22, 2010 2:45 PM
Platform Session: Section A, Monday Afternoon