[45] Evaluation of TFE3 Expression in Tumors of Microphthalmia-Associated Transcription Factor (MiTF) Family and Its Pontential Diagnostic Significance

BC Dickson, JS Brooks, TL Pasha, PJ Zhang. Pennsylvania Hospital, Philadelphia; Hospital of University of Pennsylvania, Philadelphia

Background: TFE3 is a DNA-binding factor closely related to microphthalmia-associated transcription factor (MiTF). Immunohistochemistry for TFE3 is routinely used to detect the gene fusion product in alveolar soft part sarcoma (ASPS) and Xp11-translocation renal cell carcinomas. Recently, TFE3 expression has been identified in PEComas, implying a possible role of TFE3 in the MiTF family of tumors. Our study examined TFE3 expression amongst other members of the putative MiTF group of neoplasms.
Design: Fifty-one tumors of the MITF family were available for study. These included cases of PEComa (PEC, N3), angiomyolipoma (AML, N22), metastatic malignant melanoma (MMM, N16) and clear cell sarcoma (CCS, N9). Two cases of ASPS were included for comparison. All cases were re-reviewed to verify the diagnosis. Immunohistochemistry was performed on formalin-fixed paraffin-embedded sections with goat anti-human TFE3 (1:600; sc-5958; Santa Cruz Biotechnology, CA) with heat-induced antigen retrieval in Citrate Buffer. IHC detection was performed on a DAKO Autostainer. Nuclear staining was semiquantified using the Allred scoring method, which assesses both the intensity (0-to-3) and percentage (0-to-5) of positive nuclei; cases with a combined score of 3 were arbitrarily defined as negative.
Results: Seventy-five percent of cases (38/51) tested positively, as follows: 3/4 PEC (average Allred score = 5.2), 18/22 AML (average Allred score = 4.6), 11/16 MMM (average Allred score = 4.3) and 6/9 CCS (average Allred score = 4.3). Compared to the cases of ASPS (average Allred score = 8.0), TFE3 staining was less intense and had greater variability in overall expression in the MiTF family of tumors.
Conclusions: Nuclear TFE3 can be detected in approximately 75% of the MiTF group of tumors. In addition to PEC, our data demonstrate for the first time that expression of TFE3 protein is common to all known members of the MiTF family of neoplasms including AML, CCS and MMM. While TFE3 expression tended to be variable and less intense than in ASPS, our results indicate that tumors of the MiTF family should be considered in the differential diagnosis when nuclear TFE3 reactivity is detected, particularly when the reactivity is focal and weak, and differentiated from ASPS and Xp11-translocation renal cell carcinomas.
Category: Bone & Soft Tissue

Monday, March 9, 2009 1:00 PM

Poster Session II # 12, Monday Afternoon