TFE3 (transcription factor E3) is a gene located on chromosome Xp11.2, and is a member of the microphthalmia-associated transcription factor (MITF) family. Translocations with this gene are associated with different partners in alveolar soft part sarcoma and a subset of renal cell carcinomas (Xp11.2 translocation RCC). TFE3 protein over expression can be detected by IHC in cases with a TFE3 translocation, and the expression is nuclear. The normal gene product (non-TFE3 translocation cases) is not detectable by IHC.
In a large case set (1476 cases) by Argani, et. al., TFE3 expression was demonstrated in 1/2 high-grade myxofibrosarcomas, 3/60 adrenal cortical carcinomas, and 1/15 distal bile duct carcinomas. TFE3 is a sensitive and specific marker for alveolar soft part sarcoma and Xp11.2 RCC, as it appears to be expressed in >90% of Xp11.2 translocation associated renal cell carcinomas and alveolar soft part sarcoma.
Xp11.2 RCC cases tend to express E-cadherin and CD10, while NOT expressing CK7 and EMA. Conventional clear cell RCC tend not to express E-cadherin while expressing EMA.
Photomicrographs
References:
Camparo, P., Vasiliu, V., Molinie, V., Couturier, J., Dykema, K. J., Petillo, D., et al. (2008). Renal translocation carcinomas: clinicopathologic, immunohistochemical, and gene expression profiling analysis of 31 cases with a review of the literature. The American Journal of Surgical Pathology, 32(5), 656–670. doi:10.1097/PAS.0b013e3181609914
Argani, P., Lal, P., Hutchinson, B., Lui, M. Y., Reuter, V. E., & Ladanyi, M. (2003). Aberrant nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions: a sensitive and specific immunohistochemical assay. The American Journal of Surgical Pathology, 27(6), 750–761.
Argani, P., Olgac, S., Tickoo, S. K., Goldfischer, M., Moch, H., Chan, D. Y., et al. (2007). Xp11 translocation renal cell carcinoma in adults: expanded clinical, pathologic, and genetic spectrum. The American Journal of Surgical Pathology, 31(8), 1149–1160. doi:10.1097/PAS.0b013e318031ffff
Argani, P., Antonescu, C. R., Couturier, J., Fournet, J.-C., Sciot, R., Debiec-Rychter, M., et al. (2002). PRCC-TFE3 renal carcinomas: morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(X;1)(p11.2;q21). The American Journal of Surgical Pathology, 26(12), 1553–1566.
Argani, P., Lal, P., Hutchinson, B., Lui, M. Y., Reuter, V. E., & Ladanyi, M. (2003). Aberrant nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions: a sensitive and specific immunohistochemical assay. The American Journal of Surgical Pathology, 27(6), 750–761.
Armah, H. B., & Parwani, A. V. (2010). Xp11.2 translocation renal cell carcinoma. Archives of Pathology & Laboratory Medicine, 134(1), 124–129. doi:10.1043/2008-0391-RSR.1