20q13 and cyclin D1 in ovarian carcinomas. Analysis by fluorescence in situ hybridization

In ovarian carcinomas, alterations of the chromosomal region 20q13 and the cyclin D1 gene have been described. This study has sought to determine thei r prognostic significance. Fluorescence in situ hybridization (FISH) on dis sociated nuclei and paraffin sections with DNA probes for 20q13.2 and cycli n D1, as well as immunohistochemistry (cyclin D1), were applied to formalin -fixed tissue of 69 invasive ovarian carcinomas, mainly of serous type. On dissociated nuclei 33/47 cases (70%) and on tissue sections 13/66 cases (20 %) demonstrated an increase of 20q13.2 copies. The presence of greater than or equal to 4 copies per nucleus (isolated nuclei) and greater than or equ al to 3 copies per nucleus (sections) mas associated with an adverse progno sis (Kaplan-Meier for FIGO stage III after stratification for residual tumo ur: p = 0.0049 and p = 0.03, respectively). Thirty-four out of 47 cases (72 %) showed an increase of cyclin D1 copies. Kaplan-Meier analysis for FIGO s tage III after stratification for residual tumour >2 cm or less than or equ al to 2 cm revealed an unfavourable outcome for cases with more than two cy clin D1 copies (p = 0.04). No correlation was seen between FISH and immunoh istochemistry. Multivariate analysis identified residual tumour (p = 0.0002 ), 20q13.2 gain (p = 0.0004) and cyclin D1 gain (p = 0.0343) as independent prognostic factors. It is concluded that gains of chromosomal region 20q13 .2 and the cyclin D1 gene are frequent and biologically important events, w ith prognostic relevance, in advanced ovarian carcinomas. Copyright (C) 200 0 John Wiley & Sons, Ltd.