Absence of tissue factor is characteristic of lymphoid malignancies of both T- and B-cell origin.
BACKGROUND
Thrombosis is a marker of poor prognosis in individuals with solid tumors. The expression of tissue factor (TF) on the cell surface membrane of malignant cells is a pivotal molecular link between activation of coagulation, angiogenesis, metastasis, aggressive tumor behavior and poor survival. Interestingly, thrombosis is associated with shortened survival in solid, but not in lymphoid neoplasias.


OBJECTIVE
We sought to study whether the lack of impact of thrombosis on survival in lymphoid neoplasias could be due to a lack of tumor-derived TF expression.


METHODS
We analyzed TF gene (F3) expression in lymphoid (N=114), myeloid (N=49) and solid tumor (N=856) cell lines using the publicly available dataset from the Broad-Novartis Cancer Cell Line Encyclopedia (http://www.broadinstitute.org/ccle/home), and in 90 patient-derived lymphoma samples. TF protein expression was studied by immunohistochemistry (IHC).


RESULTS
In sharp contrast to wide F3 expression in solid tumors (74.2%), F3 was absent in all low and high grade T- and B-cell lymphomas, and in most myeloid tumors, except for select acute myeloid leukemias with monocytic component. IHC confirmed the absence of TF protein in all indolent and high-grade B-cell (0/90) and T-cell (0/20) lymphomas, and acute leukemias (0/11).


CONCLUSIONS
We show that TF in lymphomas does not derive from the malignant cells, since these do not express either F3 or TF protein. Therefore, it is unlikely that thrombosis in patients with lymphoid neoplasms is secondary to tumor-derived tissue factor.
Department of Hematology, Instituto Nacional de Cancerología, México City, Mexico. Electronic address: gcesarman@gmail.com.
Gabriela
G
Cesarman-Maus
Department of Hematology and Oncology, Mayo Clinic in Arizona, USA.
Esteban
E
Braggio
Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, México City, México.
Carmen
C
Lome-Maldonado
Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, México City, México.
Ana Lilia
AL
Morales-Leyte
Department of Hematology and Oncology, Mayo Clinic in Arizona, USA.
Rafael
R
Fonseca
D001402:B-Lymphocytes / Q000473:pathology*; D020869:Gene Expression Profiling; D019337:Hematologic Neoplasms / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008221:Lymphoid Tissue / Q000473:pathology*; D011379:Prognosis; D013601:T-Lymphocytes / Q000473:pathology*; D013925:Thromboplastin / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D013927:Thrombosis / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D013925:Thromboplastin
Cancer; Hematological malignancies; Leukemias; Lymphomas; Tissue factor