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Clinical significance of loss of p16 protein by immunohistochemical staining in acute lymphoblastic leukemia

Korean Journal of Pediatrics 2008;51(1):73-77.
Published online January 15, 2008.
Clinical significance of loss of p16 protein by immunohistochemical staining in acute lymphoblastic leukemia
Hye Young Jin1, Kyoung In Kang1, Sun Young Kim1, You Sook Youn1, Joon Won Kang1, Deog Yeon Jo2, Kye Chul Kwon3, Kyung Duk Park4
1Department of Pediatrics, College of Medicine, Chungnam National University, Daejeon, Korea
2Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon, Korea
3Department of ,Clinical Laboratory Medicine, College of Medicine, Chungnam National niversity, Daejeon, Korea
4Department of Pediatrics , Korea Cancer Center Hospital, Seoul, Korea
급성림프구성백혈병에서 면역조직화학염색에 의한 p16 단백질 소실의 의의
진혜영1, 강경인1, 김선영1, 윤유숙1, 강준원1, 조덕연2, 권계철3, 박경덕4
1충남대학교 의과대학 소아과학교실
2충남대학교 의과대학 내과학교실
3충남대학교 의과대학 진단검사의학과교실
4원자력병원 소아과
Correspondence: 
Sun Young Kim, Email: sunyoung@cnuh.co.kr
Abstract
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 including childhood acute lymphoblastic leukemia (ALL), deletion and/or mutation of the p16 gene has been found. 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 loss of p16 protein confirmed by immunohistochemical staining and clinical outcomes of patients diagnosed as ALL.
Methods
: We performed an immunohistochemical staining for p16 protein 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 protein. 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)/ L. 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
: Loss of p16 protein 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 status and clinical outcomes.
Key Words: Leukemia, Lymphocytic, Acute, p16


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