Immunohistochemical Staining for p16 in Acute Lymphoblastic Leukemia.

Purpose: p16 gene, mapped to the 9p21 chromosomal region, has emerged as a candidate tumor suppressor gene in human neoplasm. It is an inhibitor of cyclin-dependent kinase and inhibits Rb phosphorylation. In a variety of tumors, deletion and/or mutation of the p16 gene has been found including childhood acute lymphoblastic leukemia (ALL). Despite their high frequency, the prognostic importance of p16 alterations is still controversial in ALL and has been reported to be either unfavorable or similar to that of other patients. We studied the correlation between p16 and clinical outcomes of patients diagnosed as ALL.

Methods: We performed an immunohistochemical staining for protein p16 in 74 cases of bone marrow biopsy slide initially diagnosed as ALL between January 1998 and December 2006. We reviewed the clinical manifestations, laboratory findings, treatment outcomes retrospectively.

Results: Of 74 slides, 12 were negative for p16. Seven were males and 5 were females with a median age at diagnosis was 5.8(1.3–18.8) years. Initial WBC were 17,225(500–403,300)/μl and by immunologic surface marker analysis, 7 patients were early pre-B CALLA(+) and 5 patients were T-cell ALL. Two patients of intermediate risk group had relapsed and died. Three patients had family history of breast cancer. Four patients died and overall survival rates were 53.5±18.7%.

Conclusion: p16 is supposed to be an independent risk factor of childhood ALL associated with poor outcomes. In clinical setting, the clinician must take into account p16 status, not only at the genomic but also at the protein level. Further clinical experience on thoroughly investigated cases will help a better understanding between p16 and clinical outcomes.