Detection of phospho‐STAT5 in mast cells: a reliable phenotypic marker of systemic mast cell disease that reflects constitutive tyrosine kinase activation

• Published in: British journal of haematology Vol. 139; no. 1; pp. 31 - 40
• Main Authors: Zuluaga Toro, Tania, Hsieh, Fred H., Bodo, Juraj, Dong, Henry Y., Hsi, Eric D.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2007; Blackwell
• Subjects: Adolescent; Adult; Aged; Base Sequence; Biological and medical sciences; Biomarkers - analysis; Bone Marrow Examination; CD2 Antigens - analysis; Cell Nucleus - chemistry; Child; Child, Preschool; Female; Flow Cytometry; Hematologic and hematopoietic diseases; Humans; Immunohistochemistry; Infant; Infant, Newborn; Interleukin-2 Receptor alpha Subunit - analysis; Male; Mast Cells - chemistry; Mast Cells - metabolism; mastocytosis; Mastocytosis, Cutaneous - enzymology; Mastocytosis, Systemic - diagnosis; Mastocytosis, Systemic - enzymology; Medical sciences; Middle Aged; Molecular Sequence Data; Mutation; Protein-Tyrosine Kinases - metabolism; Sequence Alignment; STAT5; STAT5 Transcription Factor - analysis; STAT5 Transcription Factor - genetics; Stem Cell Factor - genetics; systemic mast cell disease; Tryptases - analysis; Mastocytosis; Hematology; Enzyme; Transferases; Biological marker; systemic mast cell disease; Phenotype; Transcription factor STAT5; Systemic disease; kit; STAT5; Mast cell; Diagnosis; Protein-tyrosine kinase
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2007.06708.x

Summary Systemic mastocytosis (SM) is characterized by the abnormal proliferation and accumulation of mast cells (MCs). Constitutive activation of kit, a receptor tyrosine kinase (TK), has been associated with all types of SM. Signal transducers and activators of transcription (STATs), such as STAT5, mediate downstream kit signalling. We hypothesized that nuclear phospho‐STAT5 (pSTAT5) in MCs might reflect TK activation and would be a marker of abnormal MCs in SM. Expression of tryptase, CD25, CD2 and pSTAT5 was evaluated by immunohistochemistry (IHC) on archival cases of SM and cutaneous mastocytosis (CM). pSTAT5 was detected in 23/23 of SM and 1/9 of CM MC nuclei. 23/23 SM had CD25 + MCs. Control tissue MCs were negative for pSTAT5. Nuclear pSTAT5 in MCs from SM reflects abnormal TK activation. We propose nuclear pSTAT5 positivity in MCs as an additional minor phenotypic criterion for diagnosis of SM in future World Health Organization classification schemes.