SOX11 expression is highly specific for mantle cell lymphoma and identifies the cyclin D1-negative subtype.
BACKGROUND
Cyclin D1-negative mantle cell lymphoma is difficult to distinguish from other small B-cell lymphomas. The clinical and pathological characteristics of patients with this form of lymphoma have not been well defined. Overexpression of the transcription factor SOX11 has been observed in conventional mantle cell lymphoma. The aim of this study was to determine whether this gene is expressed in cyclin D1-negative mantle cell lymphoma and whether its detection may be useful to identify these tumors.


METHODS
The microarray database of 238 mature B-cell neoplasms was re-examined. SOX11 protein expression was investigated immunohistochemically in 12 cases of cyclin D1-negative mantle cell lymphoma, 54 cases of conventional mantle cell lymphoma, and 209 additional lymphoid neoplasms.


RESULTS
SOX11 mRNA was highly expressed in conventional and cyclin D1-negative mantle cell lymphoma and in 33% of the cases of Burkitt's lymphoma but not in any other mature lymphoid neoplasm. SOX11 nuclear protein was detected in 50 cases (93%) of conventional mantle cell lymphoma and also in the 12 cyclin D1-negative cases of mantle cell lymphoma, the six cases of lymphoblastic lymphomas, in two of eight cases of Burkitt's lymphoma, and in two of three T-prolymphocytic leukemias but was negative in the remaining lymphoid neoplasms. Cyclin D2 and D3 mRNA levels were significantly higher in cyclin D1-negative mantle cell lymphoma than in conventional mantle cell lymphoma but the protein expression was not discriminative. The clinico-pathological features and outcomes of the patients with cyclin D1-negative mantle cell lymphoma identified by SOX11 expression were similar to those of patients with conventional mantle cell lymphoma.


CONCLUSIONS
SOX11 mRNA and nuclear protein expression is a highly specific marker for both cyclin D1-positive and negative mantle cell lymphoma.
Mozos
Ana
A
Hematopathology Section, Department of Pathology and Hematology, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Spain.
Royo
Cristina
C
Hartmann
Elena
E
De Jong
Daphne
D
Baró
Cristina
C
Valera
Alexandra
A
Fu
Kai
K
Weisenburger
Dennis D
DD
Delabie
Jan
J
Chuang
Shih-Sung
SS
Jaffe
Elaine S
ES
Ruiz-Marcellan
Carmen
C
Dave
Sandeep
S
Rimsza
Lisa
L
Braziel
Rita
R
Gascoyne
Randy D
RD
Solé
Francisco
F
López-Guillermo
Armando
A
Colomer
Dolors
D
Staudt
Louis M
LM
Rosenwald
Andreas
A
Ott
German
G
Jares
Pedro
P
Campo
Elias
E
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D019938:Cyclin D1 / Q000172:deficiency*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008223:Lymphoma / Q000473:pathology; D020522:Lymphoma, Mantle-Cell / Q000737:chemistry / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D055751:SOXC Transcription Factors / Q000032:analysis* / Q000235:genetics; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C097473:SOX11 protein, human; D055751:SOXC Transcription Factors; D019938:Cyclin D1