Genetics as a diagnostic tool in sarcomatoid renal-cell cancer

Abstract

Renal-cell cancer comprises a heterogeneous group of tumors, which currently can be sub-divided into morphologically distinct entities, each characterized by a specific combination of genetic changes. Sarcomatoid transformation might occur in any of the sub-types, resulting in tumors consisting of both carcinomatous and sarcomatous components. The specific diagnosis of these neoplasms, as to tumor sub-type, is usually made on the histologic properties of the carcinomatous tissue present. However, this might not reflect the true nature of the sarcomatous component. Since the genetic changes associated with the development of the different sub-types of renal-cell cancer are well established, this knowledge might serve as a tool in diagnosing sarcomatoid tumors. Assessing the genetic constitution of the latter may lead to correct diagnosis. It may also provide valuable information about the genetic changes associated with sarcomatoid transformation. Hence we performed a genetic characterization of a case of sarcomatoid renal-cell cancer, histologically diagnosed as being of the chromophilic type. The observed genetic changes included loss of 3p, 6q, 8p, 9, 13, 14 and 17p, and gain of 5, 12 and 20, as well as a mutation in the coding region of the p53 gene. This combination of genetic changes points to clear-cell rather than chromophilic origin of the sarcomatoid tumor investigated, indicating that the genetic constitution of sarcomatoid tumors may be a more reliable indicator of tumor sub-type than histologic appearance.