Establishing germ cell origin of undifferentiated tumors by identifying gain of 12p material using comparative genomic hybridization analysis of paraffin-embedded samples

An estimated 10% of adult cancer patients present with undifferentiated car cinoma. The diagnosis of germ cell tumor (GCT) in such patients can be diff icult but has important implications for patient management. Male testicula r GCT is characterized by an isochromosome 12p, i(12p), or additional 12p m aterial, in some cases restricted to the 12p11.2-p12.1 region. A gain of 12 p material can indicate that a tumor, which may not be present in the testi s, is of germ cell origin. Formalin-fixed, paraffin-embedded samples are th e most widely available material for diagnostic analysis and retrospective studies. We have compared the identification of 12p gain in snap-frozen sam ples with corresponding paraffin-embedded material from three clearly defin ed testicular GCTs using comparative genomic hybridization analysis. In thi s preliminary study, paraffin-embedded tumor samples of uncertain histogene sis from seven patients were then analyzed. Tumor samples from three of the se patients showed a gain of 12p material, and in one patient, gain was res tricted to the 12p11.2-p12 region. The clinical picture and response to the rapy were generally consistent with the 12p status. though lack of 12p gain may not exclude a diagnosis of GCT.