Diagnosis of Primary and Metastatic Germ Cell Tumors Using Embryonic Stem Cell Transcription Factors

Abstract

Germ cell tumors (GCTs) are the most common solid tumors that affect men in the third and fourth decades of life. The vast majority of GCTs arise in the testis, with a small percentage arising at extragonadal sites including the mediastinum, brain, and sacrococcygeum. These tumors frequently present at an advanced stage with distant metastases, but even advanced disease is highly amenable to therapy and can be cured. The original diagnosis may be based on limited biopsy material and without a clinical history of a testicular mass. As a result, it can be difficult to render a confident diagnosis of GCT. Historically, the available immunohistochemical markers for GCT were limited both in sensitivity and specificity. In the last decade, insights into the biology of embryonic stem (ES) cells have led to the identification of transcription factors that are critical to the maintenance of germ cell pluripotency. These ES cell transcription factors, in particular OCT4, NANOG, SOX2 and SALL4, are also highly expressed in GCTs. These markers can be used both to support a diagnosis of GCT, as well as to determine tumor subtype. This chapter will describe the clinical and pathologic features of germ cell tumors, discuss the role of ES cell transcription factors in maintaining pluripotency in the developmental and pathologic setting, and discuss how ES cell transcription factor expression patterns can be exploited in GCT diagnosis at both primary and metastatic sites.