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in Non-Hodgkin's Lymphomas
From the Department of Pathology,*
University of
Massachusetts Medical School, Worcester, and Department of Health
Sciences and Technology,
Harvard
University-Massachusetts Institute of Technology,
Cambridge, Massachusetts
Transition of cells from quiescence to proliferation requires an
increase in the rate of protein synthesis, which is regulated
in part by two key translation initiation factors, 4E and 2
.
The expression and activity of both factors are increased transiently
when normal resting cells are stimulated to proliferate. They are
constitutively elevated in oncogene transformed cultured cells,
and overexpression of either initiation factor in rodent cells makes
them tumorigenic. In this study we investigate an association between
the expression of translation initiation factors and lymphomagenesis.
We have analyzed the expression of the protein synthesis initiation
factors 4E and 2 by immunohistochemistry in reactive lymph nodes and
several types of non-Hodgkin's lymphoma representing a wide range of
clinical behaviors based on the Revised European-American Lymphoma
behavioral classification. The study included 7 benign lymph nodes with
follicular hyperplasia, 26 indolent lymphomas (6 marginal zone
lymphomas, 7 small lymphocytic lymphomas, and 13
follicular lymphomas, grades 1 and 2), 16 moderately
aggressive lymphomas (8 mantle cell lymphomas and 8 follicular
lymphomas, grade 3), 24 aggressive lymphomas (14
large-B-cell lymphomas and 10 anaplastic large-cell lymphomas),
and 15 highly aggressive lymphomas (7 lymphoblastic lymphomas and 8
Burkitt's lymphomas). Strong expression of initiation factors 4E and
2 was demonstrated in the germinal centers of reactive follicles.
Minimal or no expression was seen in the mantle zones and surrounding
paracortices, indicating that high expression of initiation
factors 4E and 2 is associated with the active proliferation of
lymphocytes. Most cases of aggressive and highly aggressive lymphomas
showed strong expression of initiation factors 4E and 2, in
contrast to the cases of indolent and moderately aggressive
lymphoma, in which their expression was intermediate between
the germinal centers and the mantles of reactive follicles. A positive
correlation was found between the expression of both initiation factors
4E and 2 and the Revised European-American Lymphoma behavior
classification (P < 0.05). Thus,
constitutively increased expression of initiation factors 4E and 2
may play an important role in the development of lymphomas and is
correlated with their biological aggressiveness.
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