title: Is FISH a relevant prognostic tool in myelodysplastic syndromes with a normal chromosome pattern on conventional cytogenetics? A study on 57 patients.
abstract: Conventional cytogenetics (CC) at clinical diagnosis shows a normal karyotype in 40-60% of de novo myelodysplastic syndromes (MDSs). Fluorescence in situ hybridization (FISH) might detect occult aberrations in these patients. Therefore, we have used FISH to check 57 MDS patients who were karyo-typically normal on CC. At clinical diagnosis, FISH revealed a clonal abnormality in 18-28% interphase cells from nine patients, five of whom also presented the same defect on metaphase FISH. In five out of nine patients, the occult defect effected a change in the international prognostic scoring system (IPSS). An abnormal FISH pattern was significantly correlated with marrow blast cell percentage (P<10(-3)) and IPSS (P<10(-3)). Patients with an occult abnormality showed an overall survival and event-free survival significantly inferior in comparison to those of patients with normal FISH (P<10(-3), P<10(-3)). Death and AML progression were 15- and eight-fold more frequent in FISH abnormal patients. In conclusion, occult defects (1) are revealed in about 15% of CC normal MDS patients, (2) are overlooked by CC either because of the poor quality of metaphases or their submicroscopic nature, (3) are clinically relevant as they may cause a change in the IPSS category and may identify a fraction of CC normal patients with an unfavorable clinical outcome.
authors.affiliation: Division of Hematology, Policlinico San Matteo IRCCS, University of Pavia, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Bernasconi
authors.forename: P M
authors.initials: PM
authors.lastname: Cavigliano
authors.forename: M
authors.initials: M
authors.lastname: Boni
authors.forename: S
authors.initials: S
authors.lastname: Calatroni
authors.forename: C
authors.initials: C
authors.lastname: Klersy
authors.forename: I
authors.initials: I
authors.lastname: Giardini
authors.forename: B
authors.initials: B
authors.lastname: Rocca
authors.forename: N
authors.initials: N
authors.lastname: Crosetto
authors.forename: M
authors.initials: M
authors.lastname: Caresana
authors.forename: M
authors.initials: M
authors.lastname: Lazzarino
authors.forename: C
authors.initials: C
authors.lastname: Bernasconi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D018450:Disease Progression; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000628:therapy; D011379:Prognosis; D016016:Proportional Hazards Models; D012016:Reference Values; D016896:Treatment Outcome