[47] A Study of MITF/TFE Transcription Factors and Melanocytic Differentiation Markers in Angiomyolipomas

F Francis, D Nonaka. New York University School of Medicine, New York, NY

Background: Angiomyolipomas (AMLs) belong to a family of so-called perivascular epithelioid cell tumors (PEComas) that share muscular and melanocytic differentiation. Despite extensive investigation, the histogenesis and lineage of AMLs remain unclear. It has been reported that AMLs express melanocytic-associated antigens such as HMB-45 and Melan A to a greater extent than MITF and tyrosinase family of proteins for yet unknown reasons. A normal cell counterpart has not been found; however, owing to its melanocytic differentiation, AMLs have been suggested to be of neuroectodermal origin. In this study, we investigated the expression of the MiT (MITF/TFE) family of transcription factors and melanocytic differentiation markers in AMLs in order to comprehend the mechanisms of melanocytic differentiation.
Design: Twenty AMLs of renal and peri-renal regions were retrieved from the NYU Medical Center database, and immunohistochemistry studies were performed for Sox10 (neuroectodermal stem cell marker), MITF, TFE3, TFEB, TFEC, Tyrosinase, TRP1, TRP2, HMB-45 and Melan A. The extent of staining was graded as 1+ (1-25% of cells positive), 2+ (26-50%), 3+ (51-75%) and 4+ (76-100%).
Results: Sox10 was completely negative in all AMLs. MITF was expressed in 42% of the tumors with focal (1+ and 2+) reaction except for one tumor with 3+ expression. In contrast, TFE3 expression was diffuse (3+ and 4+) in all tumors. TFEB and TFEC were completely negative. HMB-45 and Melan A were expressed in all cases, and their reactions were diffuse in 42% and 26% of the tumors, respectively. Tyrosinase expression was only focal in all AMLs except for one tumor with a 3+ expression. TRP1 was variably expressed with 32% of the cases showing diffuse reaction, and TRP2 expression was focal in all tumors except for two negative cases.
Conclusions: A completely negative reaction to Sox10 in all AMLs indicates that they are probably of mesenchymal origin rather than of neural crest derivation. AMLs show full blown melanocytic differentiation, as evidenced by expression of all the melanocytic-specific markers and tyrosinase-related proteins. Diffuse expression of TFE3 in all AMLs in comparison to focal MITF reaction in 42% of the tumors suggests that TFE3, probably in conjunction with MITF, plays a major role in the melanocytic differentiation in AMLs.
Category: Bone & Soft Tissue

Monday, March 9, 2009 9:15 AM

Platform Session: Section E, Monday Morning