Cytogenetic Analysis and FISH in the Evaluation of Patients with MDS: A Retrospective Analysis of Concordance Rate, Utility and Benefit of Performing Both Studies Simultaneously

Background: The Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders, characterized by cytopenia, and risk of progression to acute leukemia. Chromosomal abnormalities are detected in 40–60%of patients with MDS. Cytogenetic findings are critical for diagnosis, prognosis and monitoring therapy. FISH has been reported to detect occult clonal abnormalities in 15–7.8% of karotypically normal patients in some studies, but found to be of limited value in others. We sought to evaluate whether FISH can be a valuable diagnostic/prognostic adjunct to conventional cytogenetic (CC) analysis.

Methods: Since the implementation of FISH panel at our institution, we have identified 62 MDS patients who had both CC and FISH panel tests performed simultaneously. Our FISH panel was designed specifically to detect abnormalities in chromosomes 5, 7, 8, 11 and 20.

Results: In these patients, concordance between the 2 methods was noted in 43 patients (69.3%). Clonal chromosomal abnormalities were detected by CC in 36 patients (58 %). FISH defined additional clones in 7/26 patients with normal and 3/36 patients with an abnormal karyotype increasing the detection rate by 16%. Importantly, 9/36 patients with abnormal CC had clonal abnormalities in chromosome regions not analyzed, thus not detected, by our FISH panel.

To further evaluate the prognostic significance of the additional clones detected by FISH, we calculated and compared the IPSS risk category for the 10 patients identified with discordant results utilizing data derived from CC and FISH. 3 patients had no change in their IPSS scores, 7 patients had an upgrade in their IPSS scores as follows: from low to Int-1: 4, Int-1 to Int-2: 2, and Int-2 to High: 1. If one were to apply NCCN guidelines with regard to treatment options according to IPSS risk categories, FISH upgraded scores could potentially result in change of therapy in 2/10 patients with discrepancy, and in 2/62 (3%) patients altogether.

Conclusion: Our results suggest that FISH has the potential of increasing the rate of detecting chromosomal abnormalities in complete CC studies that have failed to reveal clonal abnormalities. However, the practical impact of finding such clones seems to be very low resulting in potential change of clinical management in only 3% of patients. Furthermore, in cases with identified cytogenetic abnormalities, FISH was of limited benefit. Our series is small and retrospective in nature; prospective studies addressing the utility, benefit, and cost justification of this method are needed.