Expression of signal transducer and activator of transcription 3 (STAT3) in primary central nervous system diffuse large B-cell lymphoma: a retrospective analysis of 17 cases.
Most primary central nervous system lymphomas (PCNSL) occurring in immunocompetent patients are diffuse large B-cell lymphomas (DLBCL), characterized by poor prognosis. An activated B-cell (ABC) origin of PCNSL has been postulated based on bcl-6 and MUM-1 expression by majority of these tumors. ABC DLBCL has been functionally subdivided using gene expression profiling and immunohistochemical analysis into STAT3-high and STAT-3 low subsets. A potentially crucial difference between STAT3-high and STAT3-low ABC DLBCL is in the expression of bcl-2 family members. STAT3-high cases are generally bcl-2 low and STAT3-low cases show higher expression of bcl-2. Further mechanisms such as activation of nuclear factor-kappa B (NF-κB) activation seem to be responsible for upregulation of bcl-2 in ABC subtype of DLBCL with an adverse outcome. As deregulation of STAT-3 pathway is known to play a critical role in ABC DLBCL and majority of the PCNSL are of the ABC subtype we studied the immunohistochemical expression of STAT-3 proteins in PCNSL along with other traditional markers (CD10, bcl-6, MUM-1 and bcl-2) in 17 cases of PCNSL occurring in immunocompetent patients. Despite lack of STAT3 expression in all our cases, majority (70%) of the patients with bcl-2 positive PCNSL had an adverse outcome similar to that reported in systemic lymphomas of ABC subtype. Based on our observations we propose that PCNSL represents a distinct subset of ABC diffuse large B-cell lymphomas with low STAT3 expression and perhaps mechanisms other than interaction of STAT-3 and NF-κB pathways may play a role in upregulation of bcl-2 in PCNSL. To the best of our knowledge expression of STAT-3 protein in PCNSL which represents a distinct anatomical subset of ABC DLBCL with a dismal prognosis has not been studied before.
Vajpayee
Neerja
N
Division of Hematopathology, Department of Pathology, SUNY Upstate Medical University, Syracuse, NY, USA. vajpayen@upstate.edu
Hussain
Juhi
J
Tolocica
Ioana
I
Hutchison
Robert E
RE
Gajra
Ajeet
A
D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D050796:STAT3 Transcription Factor / Q000096:biosynthesis*; D016019:Survival Analysis
D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
Blood. 2003 Jan 1;101(1):78-84
12393466
Clin Cancer Res. 2006 Feb 15;12(4):1152-6
16489068
Mod Pathol. 2010 Feb;23(2):235-43
19935644
Oncogene. 2000 May 15;19(21):2474-88
10851046
Blood. 1996 Jan 1;87(1):265-72
8547651
J Cell Physiol. 2003 Nov;197(2):157-68
14502555
J Clin Oncol. 2006 Feb 20;24(6):961-8
16418494
Blood. 1997 Jul 1;90(1):244-51
9207459
Clin Cancer Res. 2003 Mar;9(3):1063-9
12631608
Cancer. 2008 Jan 1;112(1):151-6
17999414
Blood. 2004 Jan 1;103(1):275-82
14504078
Am J Surg Pathol. 2004 Apr;28(4):464-70
15087665
Clin Neuropathol. 2008 Jan-Feb;27(1):13-20
18257470
Blood. 2006 Jan 1;107(1):190-6
16150948
Blood. 2008 Apr 1;111(7):3701-13
18160665
Am J Clin Pathol. 2007 May;127(5):770-8
17439836
Blood. 2007 Apr 1;109(7):2700-7
17119127