Prognostic significance of p16(INK4a) immunocytochemistry in adult ALL with standard risk karyotype

The p16(INK4a) gene is frequently inactivated in acute lymphoblastic leukem ia (ALL), by homozygous deletion. However, p16(INK4a) protein expression al so varies widely in ALL blasts. We investigated the p16(INK4a) protein expr ession by immunocytochemistry (ICC) analysis in 76 cases adult ALL. We obse rved a great variation of the percentage of ICC-positive leukemic cells bet ween samples even in which FISH analysis did not find p16(INK4a) gene delet ion. All patients carrying a p16(INK4a) gene homozygous deletion were also negative by ICC. ALL with negative p16(INK4a) ICC were more frequently of T lineage, but no significant differences for white blood cell count, presen ce of bulky disease, karyotype, hemoglobin level, complete remission rate, overall and event-free survival (EFS) were found. However overall survival and EFS were significantly lower in patients negative by ICC, when analysis was performed in ALL with standard risk karyotype. We also analyzed sequen tially at diagnosis and relapse nine cases and observed that one case lost p16(INK4a) expression between diagnosis and relapse, but that on the contra ry three other samples showed increased expression at relapse. These findin gs suggest that p16(INK4a) ICC and deletion analysis provide distinct infor mation about ALL cells and that the simple ICC method may be of prognostic value in standard risk adult ALL.