Significance And Expression Of Survivin,Ki-67 And PCNA Protein In Nonhodgkin's Lymphoma

Objection: cell-immortalization and apoptosis-hindered are the tumorigenic foundation. The research about the proliferation and apoptosis of NHL tumor cells, is helpful to reveal the mechanism of NHL's happening and development, understand the tumor's bionomics, provide valuable targets for the diagnosis,treatment and prognosis of the tumor. Survivin is one of the members of apoptosis inhibitor protein family, expressed in most tumor tissues, which may inhibit the apoptosis of tumor cells, promote the proliferation of tumor cells, participate in angiogenesis, and is connected with the malignant degrees and unfavourable prognosis of some tumors. This study chose frequent pathological types in China, according to the epidemiological characteristic of NHL in China. We detected the expression of Survivin in NHL with immunohistochemistry, approaching the effective and clinical significance of the Survivin gene in the pathogenesis of NHL with different malignant degrees. The detection of these targets may improve the judgement of the prognosis of NHL patients , guide clinical treat, reveal the molecular pathogenesis of lymphoma, and provide a new thought for the diagnosis,the judgement to the prognosis and gene therapy of NHL.Materials and Methods: The paraffin samples of 52 patients who had been in Shandong Provincial Hospital during the period from January 2001 to October 2002 with complete data in hospital were chosen. Also 12 cases with reactive hyperplasia of lymph node (RH) were chosen as control group. According to the principle of antigen-antibody reaction we detected the expression of Survivin in 52 cases with NHL and 12 cases with reactive hyperplasia of lymph node with rabbit anti-human Survivin polyclonal antibody and the SP method of immunohistochemistry. Finally we did statistical analysis combining with clinical and pathological data.Results: 1. The expression rate of Survivin in RH is 1.25%, the one in indolent lymphoma is 7.15%. By comparison there is significant change in the expression rates of both groups (P<0.01) .The expression rate of Survivin in invasive lymphoma is 50.14%, which is obviously higher than that in indolent lymphoma (P<0.01) .2. The expression rate of Survivin in NHL patients who were younger-than-50 (including 50) is 34.02%, the one in NHL patients who were older-than-50 is 37.86%. By comparison there is not significant change in the expression rates of both groups(P>0.05) .3. The expression rates of Survivin in NHL of males are 33.71% ,the one in females is 39.91%, by comparison the former is less than the latter. But the statistical analysis indicates that the expression of Survivin has no relation with the gender(P>0.05) .4. The expression rate of Survivin in NHL of stage I and stage II is 32.10%, the one of stage III and stage IV is 40.74%, the former is less than the latter. But the statistical analysis indicates that there is no significant change (P>0.05) ,revealing the expression of Survivin has no relation with clinical staging.5. The expression rate of Survivin in NHL of A group is 33.07%, the one of B group is 39.12% . The expression of Survivin has no relation with whether there is general symptom or not (P>0.05) .6. The expression of Survivin has no relation with the immunizing type of NHL. The expression rate of Survivin in NHL of T cell is 31.16%, the one of B cell is 38.92%. By comparison there is not significant change in the expression rates of both groups (P>0.05) . 7. The expression rate of Survivin in NHL whose primary position is lymph node is 37.08%, the one in NHL whose primary position is out of lymph node is 34.74%, the expression of Survivin has no relation with the primary position of lymphoma.8. The expression rates of of Survivin in NHL patients whose LDH are lower than 250u/L is 20.38%, the expression rate of Survivin in NHL patients whose LDH are higher than 250u/L is 48.56% , the former is obviously lower than the latter(P<0.01 ) .9. The mean survival time of those patients whose expression rates of Survivin are lower than 25% is 30.2 months, the one of those patients whose expression rates of Survivin are higher than 25% is 17.6 months. By comparing the mean survival time of the group whose expression rates of Survivin are higher than 25% with that whose expression rates of Survivin are lower than 25% ,the analysis indicated the former is shorter, the survival curves of Kaplan-Meier are significantly different.Conclusion: The expression rate of Survivin in RH is obviously lower than the ones in NHL, the expression rate in invasive lymphoma is obviously higher than that in indolent lymphoma. The expression of Survivin in NHL have no relations with the sex, the age, clinical staging, whether there are general symptom or not, the origin of tumor cell and the primary position of lymphoma. The expression of Survivin in NHL is connected with the level of LDH. By comparing the mean survival time of the group whose expression rates of Survivin are higher with that whose expression rates of Survivin are lower, the analysis indicates the former is shorter. Survivin is relevant with the happening and development of NHL, and provide proofs to judge the prognosis. Objection: The infinite amplification of cell clone is the direct factor to result in malignant tumors, NHL is a type of lymphoid malignant tumor with high heterogeneity. The research about the proliferation and apoptosis of NHL tumor cells is helpful to reveal the mechanism of NHL's happening and development. An antigen of Ki-67 is one kind of nucleus antigen, expressing in the proliferating-nucleus only, regarded as the marker to reflect the action of cell proliferation now. The expression of Ki-67 is connected with cell cycle, which is essential to cell proliferation. PCNA is one kind of nuclear protein, participating in the duplication of DNA and the regulation of cell cycle, which has a close relation with the proliferating cycles. The study chose 52 patients with NHL whose pathological types were frequent in China. We detected the expression of Ki-67 and PCNA in NHL with immunohistochemistry, approaching the effective and clinical significance of the genes in the pathogenesis of NHL with different malignant degrees. The detection of these targets may improve the judgement of the prognosis of NHL patients , guide clinical treat, reveal the molecule pathogenesis of lymphoma, and provide a new thought for the diagnosis,the judgement to the prognosis and gene therapy of NHL.Materials and Methods: The paraffin samples of 52 patients who had been in Shandong Provincial Hospital during January 2001 to October 2002 with complete data in hospital were chosen. Also 12 cases with reactive hyperplasia of lymph node (RH)were chosen as control group. According to the principle of antigen-antibody reaction we detected the expression of Ki-67 and PCNA in 52 cases with NHL and 12 cases with reactive hyperplasia of lymph node with mouse anti-human Ki-67 monoclonal antibody, mouse anti-human PCNA monoclonal antibody and the SP method of immunohistochemistry. Finally we did statistical analysis combining with clinical and pathological data.Results: 1. The expression rate of Ki-67 in RH is 10.11%, the one in indolent lymphoma is 18.4%. By comparison there is significant change in the expression rates of both groups (P<0.05) .The expression rate of Ki-67 in invasive lymphoma is 46.14%, which is obviously higher than that in indolent lymphoma (P<0.01) . The expression rate of PCNA in RH is 14.22%, the one in indolent lymphoma is 25.95%. By comparison there is significant change in the expression rates of both groups (P<0.05 ) . The expression rate of PCNA in invasive lymphoma is 50.64%, which is obviously higher than that in indolent lymphoma (P<0.01) .2. The expression rate of Ki-67 in NHL patients who were younger-than-50 (including 50) is 36.20%, the one in NHL patients who were older-than-50 is 37.81%. By comparison there is not significant change in the expression rates of both groups( P > 0.05 ) . The expression rate of PCNA in NHL patients who were younger-than-50 (including 50) is 43.37%, the one in NHL patients who were older-than-50 is 41.88%. By comparison there is not significant change in the expression rates of both groups (P>0.05) .3. The expression rates of Ki-67 and PCNA in NHL of males are 35.35% and 40.69%, the ones in females are 39.82% and 45.57%, by comparison the former is less than the latter. But the statistical analysis indicates that the expression of Ki-67 and PCNA have no relation with the gender.4. The expression rates of Ki-67 and PCNA in NHL of stage I and stage II are 35.99% and 39.34%, the ones of stage III and stage IV are 38.33% and 46.33%, the former is less than the latter. But the statistical analysis indicates that there is no significant change (P>0.05) ,revealing the expression of Ki-67 and PCNA have no relation with clinical staging. 5. The expression rates of Ki-67 and PCNA in NHL of A group are 35.68% and 40.10%, the one of B group are 38.46% and 45.03% . The expression of Ki-67 and PCNA have no relation with whether there are general symptom or not.6. The expression of Ki-67 and PCNA has no relation with the immunizing typing of NHL. The expression rates of Ki-67 and PCNA in NHL of T cell are 39.24% and 42.57%, the ones of B cell are 35.82% and 42.56%.7. The expression rates of Ki-67 and PCNA in NHL whose primary position is lymph node are 37.60% and 46.05%, the ones in NHL whose primary position is out of lymph node are 36.35% and 37.81%, the expression of Ki-67 and PCNA have no relation with the primary position of lymphoma.8. The expression rates of Ki-67 and PCNA in NHL whose LDH are lower than 250u/L are 27.19% and 30.97%, the expression rates of Ki-67 and PCNA in NHL whose LDH are higher than 250u/L are 44.90% and 51.76%, the former is obviously lower than the latter.9. The mean survival time of those patients, whose expression rates of Ki-67 are lower than 25% is 28.8 months, the one of those patients whose expression rates of Ki-67 is higher than 25% is 18.4 months. The mean survival time of those patients whose expression rates of PCNA are lower 25% is 29.5 months, the one of those patients whose expression rates of PCNA are higher than 25% is 18.9 months. By comparing the mean survival time of the group whose expression rates of Ki-67 and PCNA are higher than 25% with that whose expression rates of Ki-67 and PCNA are lower than 25% ,the analysis indicated the former is shorter, the survival curves of Kaplan-Meier are significantly different.10. The expression of Ki-67 and PCNA exists the trend of synchronizing change, Pearson correlated test displays that the LI of Ki-67 is positive correlation with the LI of PCNA (r=0.7886) .Conclusion: The expression rates of Ki-67 and PCNA in RH are obviously lower than the ones in NHL, the expression rate in invasive lymphoma is obviously higher than that in indolent lymphoma. The expression of Ki-67 and PCNA in NHL exist positive correlation. The expression of Ki-67 and PCNA in NHL have no relations with the sex, the age, clinical staging, whether there are general symptom or not, the origin of tumor cell and the primary position of lymphoma. The expression of Ki-67 and PCNA in NHL is connected with the level of LDH. By comparing the mean survival time of the group whose expression rates of Ki-67 and PCNA are higher with that whose expression rates of Ki-67 and PCNA are lower, the analysis indicates the former is shorter. Ki-67 and PCNA are relevant with the happening and development of NHL, and provide proofs to judge the prognosis.