Expression of anaplastic lymphoma kinase, tyrosine-phosphorylated STAT3, and associated factors in pediatric anaplastic large cell lymphoma: A report from the children's oncology group.
In anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK) activates (phosphorylates) signal transducer and activator of transcription 3 (STAT3) with subsequent cytoplasmic expression, in some cases, of survivin and tissue inhibitor of metalloprotease 1 (TIMP1). These are inhibitors of apoptosis and negative prognostic factors. CD56 is also a negative prognostic marker in ALCL. We assayed 40 cases of predominantly ALK+ pediatric ALCL for pSTAT3, survivin, TIMP1, and CD56 using immunohistochemical analysis. The patients were derived from a Pediatric Oncology Group treatment protocol that showed 72% event-free survival at 4 years for ALCL. The results show that in advanced-stage pediatric ALCL, although most tumors express ALK and a majority show activated STAT3, cytoplasmic localization of survivin and TIMP1 is not frequent, nor is expression of CD56. This may help, in part, explain the relatively good prognosis of pediatric ALCL.
Nasr
Michel R
MR
Department of Pathology, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
Laver
Joseph H
JH
Chang
Myron
M
Hutchison
Robert E
RE
D000293:Adolescent; D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D019002:CD56 Antigen / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D051034:Inhibitor of Apoptosis Proteins; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry* / Q000401:mortality; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis; D009363:Neoplasm Proteins / Q000032:analysis; D011505:Protein-Tyrosine Kinases / Q000032:analysis*; D020794:Receptor Protein-Tyrosine Kinases; D050796:STAT3 Transcription Factor / Q000032:analysis*; D000077022:Survivin; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis
C107489:BIRC5 protein, human; D019002:CD56 Antigen; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; D000077022:Survivin; D019715:Tissue Inhibitor of Metalloproteinase-1; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases