[1318] Fluorescence In Situ Hybridization (FISH) and Cytogenetic (CG) Karyotype Studies in Myelodysplastic Syndrome (MDS): One or Both?

DK Durnick, RP Ketterling, JD Hoyer, DP Steensma, DL Van Dyke, JM Hodnefield, RA Knudson, CA Hanson. Mayo Clinic, Rochester, MN

Background: MDS is characterized by cytopenias, dysplasia, ineffective hematopoiesis, and risk of progression to AML. The current standard in evaluating suspected MDS is bone marrow (BM) morphology and CG analyses, but MDS-FISH studies are also often requested. The aim of this study is to determine the roles of CG and MDS-FISH analyses in the diagnosis of MDS and also in identifying patients with del(5q) for potential lenalidomide therapy.
Design: 435 potential MDS patients from Mayo Clinic were identified with BM, CG, and interphase FISH analyses (8/2006-7/2009). FISH probes used included an MDS-FISH panel [inv(3)(q21q26.2), del(5q), -7/del(7q), +8, del(13q), del(20q)] in 280 cases and selected probes in 155 cases. 20 cases were excluded due to lack of testing with the appropriate FISH probe.

FISH NormalFISH Abnormal
CG Normal21310
CG: ≥2 Metaphases Abnormal16122
CG: 1 Metaphase Abnormal459

The 10 normal CG/abnormal FISH cases included: 5 MDS (3 RCMD; 2 RAEB-2), 2 AML, 2 CMML, and 1 normal BM (20q- in 6% cells). The anomalies found by FISH: -7/7q- (n=4), +3/+3q26 (n=2), +8 (n=2), 20q- (n=2), 5q- (n=1). The 16 abnormal CG/normal FISH cases included: -7/7q- (n=6), 20q- (n=4), complex (n=4) and +8 (n=1). The use of MDS-FISH when only 1 abnormal metaphase is found by CG remains of uncertain clinical significance.

FISH: No 5q-FISH with 5q-
CG: No 5q-38121
CG with 5q-924

24 cases had del(5q) by both CG and FISH, 9 by CG, and 21 by FISH only. The 9 positive by CG: 4 complex CG karyotypes; 5 with 1 abnormal metaphase [del(5q)]. The 21 positive by FISH: no del(5q) by CG; 1 was normal.
Conclusions: Although MDS-FISH is thought to increase detection of MDS, no studies have looked at how to effectively use CG and FISH studies in the evaluation of the potential MDS patient. Our results show good correlation between CG (normal and ≥2 metaphases) and FISH with agreement in 335/361 (93%). In addition, FISH identified 10 patients with anomalies not found by CG. However, 9/10 had conclusive MDS/preceding MDS diagnoses; 1 had a normal BM with a very low % of 20q- identified by FISH. In our study 21/54 patients with a del(5q) were identified only by FISH. These data suggest there is limited utility for MDS-FISH panel at diagnosis when chromosome studies are successful. However, once a diagnosis of MDS is made and CG does not show a del(5q), then it is appropriate to do FISH studies only for del(5q) to ensure its detection.
Category: Hematopathology

Monday, March 22, 2010 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 179, Monday Morning


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