INTERPHASE FLUORESCENCE IN-SITU HYBRIDIZATION IMPROVES THE DETECTION OF MALIGNANT-CELLS IN EFFUSIONS FROM BREAST-CANCER PATIENTS

In diagnostic evaluation of effusions, difficulties are encountered wh en atypical reactive mesothelial cells have to be differentiated from malignant cells. We tested the impact of fluorescence in situ hybridiz ation (FISH) to identify metastatic cells in breast cancer effusions b y detection of numerical chromosomal changes. Pleural and ascitic flui d samples (n=57) from 41 breast cancer patients were concomitantly eva luated by routine cytology and FISH, using centromere-specific probes representing chromosomes 7, 11, 12, 17 and 18. After setting stringent cut-off levels deduced from non-malignant control effusions (n=9), th e rates of cells with true aneuploidy were determined in each effusion sample from breast cancer patients. The occurrence of aneuploid cells , as detected by FISH and indicative of malignancy, was correlated wit h the cytological findings. Routine cytology revealed malignancy in 60 % of effusions. Using FISH, aneuploid cell populations could be observ ed in 94% of cytologically positive and in 48% of cytologically negati ve effusions, thus reverting diagnosis to malignancy. To confirm malig nancy in cases with a low frequency of aneuploid cells, two-colour FIS H was additionally performed and indeed showed heterogeneous chromosom al aneuploidy within single nuclei. We conclude that FISH is a valuabl e tool in the diagnosis of malignancy and may serve as an adjunct to r outine cytological examination, as demonstrated here for breast cancer effusions.