[1297] Immunoexpression of Cell Cycle Molecules Participated in P27^Kip1 Degradation in B-Cell Lymphomas

C Sirinian, A Symeonidis, N Giannakoulas, H Vlotinou, M Melachrinou. Medical School, University of Patras, Patras, Greece

Background: Evidences suggest that deregulation of p27 plays a critical role in the pathogenesis of many human tumors. The inactivation of p27 is achieved through either degradation via the ubiquitin-mediated proteolytic pathway or sequestration by cyclins D. Skp2, a component of ubiquitin-ligase SCF complex, interacts with p27 only when it is phosphorylated on Thr-187 (Pp27) by cyclin E/CDK2 and/or cyclin A/CDK2. We examined the expression of skp2, p27, Pp27, cyclin E, cyclin A and CDK2 in B-cell lymphomas to determine whether alterations in their relative levels are associated with changes in cell proliferation and lymphoma groups.
Design: Formalin-fixed, paraffin-embedded tissue from 105 cases of B-cell lymphomas [Group A: 66 DLBCLs, Group B: 39 small B-cell lymphomas (9 FLs {3 Grade 1, 6 Grade 2}, 8 MCLs {no blastoid}, 12 MZLs, 10 SLLs] were immunostained with antibodies for skp2, p27, Pp27, cyclin E, cyclin A, CDK2 and Ki67 using Envision detection kit. Clinical data were available for 52 cases [29/Group A, 23/Group B].
Results: Group A showed a significant higher immunoexpression of skp2 (30.07% vs 5.32%), Pp27 (34.15% vs 6.79%), cyclin E (21.33% vs 5.19%), cyclin A (22.89% vs 5.31%) and CDK2 (23.11% vs 6.80%), and a higher proliferation index (PI) (69.08% vs 17.27%) as well, compared to Group B. On the contrary, Group B demonstrated a significant more intense immunoreaction for p27 (64.46% vs 31.18%) (p < 0.05). In both groups was detected a positive correlation between 1) skp2 and PI, 2) cyclin A and PI, 3) CDK2 and PI, 4) cyclin E and cyclin A, 5) cyclin A and CDK2. In Group A was identified a positive correlation between 1) p27 and Pp27, 2) skp2 and cyclin A, 3) skp2 and CDK2, 4) cyclin E and CDK2. In Group B was observed a positive correlation between 1) skp2 and Pp27, 2) Pp27 and a) PI, b) cyclin A and c) CDK2 (p < 0.05). The studied molecules were not related with patients' prognosis.
Conclusions: Our findings suggest the p27 degradative function of Skp2 in small B-cell lymphomas. Although this relationship is not detected in DLBCLs, the overexpression of P-p27 is indicative that the proteolysis of p27 has been triggered. Our data demonstrate a positive correlation between Skp2 expression and PI in B-cell lymphomas. The positive relationship between P-p27 and PI in small B-cell lymphomas is consistent with the findings of previous studies which detected the expression of P-p27 in proliferating cells.
Category: Hematopathology

Tuesday, March 10, 2009 9:30 AM

Poster Session III # 121, Tuesday Morning