Xp11.2 Translocation Renal Cell Carcinoma(RCC) in Adults A TMA Study of 120 RCC Cases
M Zhong, J Habermann, N Andraws, A Pavlenko, M Jordan, M Hameed. UMDNJ-New Jersey Medical School, Newark, NJ
Background: Xp11.2 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 diagnosis of Xp11.2 translocation carcinomas has also been reported in elderly patients. This 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 proven as a sensitive and specific method for the diagnosis of the Xp11.2 translocation RCC, however, the weaker nuclear stain remains problematic for interpretation.
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). Immunohistochemical analysis was performed on TMA using TFE3 (P-16) antibody. The staining intensity was graded according to previous report (AJSP 2003; 27:750). We have investigated few cases with strong and weaker nuclear stain using RT-PCR( 1 case with weaker nuclear stain and 2 cases with strong nuclear stain) and Western blot analysis (2 cases with no staining, 4 cases with weaker nuclear stain and 2 cases with strong nuclear stain).
Results: Among the 120 RCC, 11(9.2%) cases were TFE3 positive (strong nuclear stain) with a mean age of 54 (range 31-77). There were 6 females and 5 males. The percentage of positive cases in different age groups, were 20% (3/15) in the age group 18-40; 5.9%(3/51) in the age group 41-60 and 9.3%(5/54) in the age group older than 60. No TFE3 fusion transcripts (ASPL, PRCC, CLTC, PSF and Nono) were detected by RT-PCR in the tested case with weak nuclear stain. The two tested cases with strong nuclear staining showed the ASPL-TFE3 transcript. Full length TFE3 protein was detected by western blot in all 4 tested cases with weaker nuclear staining.
Conclusions: 1) Xp11.2 translocation RCC is not an uncommon neoplasm. The incidence in this group of 120 patients is 9.2% in adults and up to 20% in patients between 18-40 years. 2) TFE3(P-16) IHC is a valuable 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.
Category: Genitourinary (including renal tumors)
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 134, Wednesday Afternoon