Síndromes mielodisplásticas [manuscrito] : caracterizacão morfológica e imunohistoquímica quanto a expressão da proteína p 53

Abstract

Summary The p53 gene is currenuy thought to be a tumor suppressor gene, and its alterauons have been suggested to be involved m the pathogenesis of several human malignajicies. The piirpose of fhe present study was fhe evaluation of histológica! findings and the uiununohistochemical study ofp53 egression on bone marrow biopsy from uiirty- three patients in which a myelodysplasuc syndrome (MDS) was diagnosed. Forty- three bone marrow biopsies were reü-ospecüvely reviewed, and relationship among the different histological parajmeters as weU as clinicopafhological correlations were looked for. Histological analysis showed in 78,8% of cases a hypercellular, in 12,1% a hypocellular and in 9,1% a norniocellular bone marrow. Dysraegakaryopoiesis was the inost prominent abnormality of the hematopoietic series, detected in 72,7% of cases. Abnormal localization of immature precursors occurred in 39,4% of patients and increase in reticulin fibers occurred in 34,4%. The frequency oflymphoid nodules in our cases (27.3%) was higher fhan that reported by others with no relauonship with age, but significanuy related to Üückenmg of Uie reticulin network . Nuclear accumulaüon ofp53 protein was foimd m 15,2% offhe cases whereas control subjects were imiformly negaüve for p53 protein. All the five MDS cases that exhibited positive p53 reaction had some kind of disease progression, namely a more advanced FAB subtype and/or acute leukenua. A p53 immunoreactivity was therefore significanuy related to biological aggressiveness and progression of the disease. The results suggest that p53 mutauons may contribute, albeit rarely, to the development of MDS and, once present, may confer a growth advantage to myeloid cells and therefore is useful for predicting the evoluüon. MDS is heterogeneous not only in its phenotype but also in the Kciolecular niechanism of its genesis and progression. More extended and detailed study is necessary to understand the molecular basis of MDS development. The major aim is a more specific and effective treatment of these pauents.