Study on Expression of Survivin Gene and Its Relations with Cell Apoptosis and Proliferation in Nasal and Nasal Type NK/T Cell Lymphoma
|Keywords||NK/T cell lymphoma Survivin gene Apoptosis Proliferation cell nuclear antigen|
Objective: Extranodal NK/T cell lymphoma (nasal, nasal type), established in the new lymphoma classification system released by the World Health Organization (WHO) in 1997, is a highly invasive malignant tumor closely related with Epstein-Barr virus (EBV). Its incidence in China is among the highest in the world and its pathogenesis not entirely clear. Apoptosis is gene programmed cell death (PCD) and the imbalance between it and cell proliferation is closely related to the development and progression of tumors. Survivin is apoptosis inhibitor gene, discovered in 1997, which fights apoptosis mainly by suppressing the activities of Casapase-3 and Caspase-7. There have been no recent reports on study of relationship between Survivin gene expression and cell apoptosis and proliferation in NK/T cell lymphoma. This research studies cell apoptosis, proliferation cell nuclear antigen (PCNA) as well as Survivin expression rate so as to understand then-roles in the development and progression of NK/T cell lymphoma.Methods: (1). 25 cases of nasal-pharyngeal NK/T cell lymphoma underwent histomorphological and CD45RO, CD3, CD20 immunohistochemical analysis. IN addition, immunohistochemical S-P method was used to detect TIA-1, granzyme B and insituhybridization (ISH) method to detect mRNA encoding EBV (EBER 1/2). The diagnosis was based on the 1997 WHO classification system. (2). TdT-mediated dUTP nick end labeling (TUNEL) and immunohistochemistry were used to study cell apoptosis, PCNA, Survivin gene expression in 25 nasal and nasal type NK/T cell lymphomas and 10 reactive lymphoid tissues. The number of positive cells in every 1000 tumor cells were counted as the Survivin positive rate, proliferative index (PI) and apoptotic index (AI) respectively.Results: (1) CD45RO, CD3 and TIA-1 were positive in the 25 cases (100%), granzyme B was positive in the 22 cases (88.00%), EBER 1/2 positive in 21 cases (84.00%) while CD20 negative in all the 25 cases (100%). (2) AI and PI averaged (1.92% +0.86%) and (41.48%+5.10%) respectively in the 25 NK/T cell lymphomas and (6.70%+ 1.89%) and (20.10% +2.77%) in the 10 reactive lymphoid tissues. Compared with reactive lymphoid tissues, AI was significantly reduced in NK/T cell lymphoma (t= 10.80,P<0.01) while PI significantly increased (t=12.39,P<0.01). In addition, in NK/T cell lymphoma, AI and PI were positively related (r=0.69,.P<0.01). (3) Survivin expression was positive in 17 NK/T cell lymphomas (68.00%) while no expression of Survivin was detected in the 10 reactive lymphoid tissues (P<0.01). (4) AI in nasal NK/T cell lymphoma cells with positive expression of Survivin was significantly lower than that with negative Survivin (1.71%+0.61% vs 2.29%+ 0.72%) whereas PI was significantly higher (43.35% + 4.80% vs 37.50%+2.90%). Both differences were significant (t= 2.08, P<0.05 and t=3.16, P<0.01).Conclusions: In NK/T cell lymphoma, cell apoptosis is reduced while cell proliferation increased and Survivin gene expression is up-regulated. Survivin gene may play a role in the pathogenesis of NK/T cell lymphoma tumor by influencing cell apoptosis and proliferation. AI, PI and Survivin expression positive rate may reflect tumor growth dynamics and its biological behaviors and therefore, can be used as important indices in the diagnosis, treatment and prognosis prediction of NK/T cell lymphoma.