Evaluation of chromosome 12 copy number in ovarian granulosa cell tumors using interphase cytogenetics

Trisomy 12 is frequently observed in karyotypes of ovarian sex cord-stromal tumors, including adult and juvenile granulosa cell tumors (AGCTs and JGCTs). We assessed the ability to detect this abnormality in deparaffinized tissue sections of 19 ovarian GCTs (17 AGCTs, two JGCTs) and in one fibrothecoma by simultaneous in situ hybridization with fluorescent-labeled centromeric probes to chromosomes 12 (fluorescein isothiocyanate conjugated) and 17 (rhodamine conjugated). In order to quantitate the artifact introduced by nuclear slicing, such analyses were performed both on intact tissue sections and on cytospins of nuclei prepared by enzymatic dissociation from the corresponding tissue block. The series was also evaluated for numerical abnormalities of chromosome X, a less common cytogenetic finding in GCT. Twelve of 19 cases (63%) displayed evidence of trisomy 12 (defined as signal gain in > or = 10% of nuclei) in the intact section, the cytospin, or both. Trisomy for chromosome 17 was present in one case, and trisomy X was present in two cases. In tissue sections the incidence of signal gain for the chromosome 12 probe varied from 0-45% of nuclei (mean 19%). In cytospin preparations, the percentage signal gain for chromosome 12 ranged from 0 to 84% (mean 33%). This study supports the presence of trisomy 12 as a common, but not defining, cytogenetic anomaly in ovarian GCTs. Its presence, however, within only a minority of tumor cells may be partly explained by slicing artifact associated with intact tissue sections, although partial involvement of intact nuclei suggests that trisomy 12 may also be encountered as a heterogeneous abnormality within neoplastic populations of GCTs.