The Potential Role of p27, Skp2, and PTEN Expression in Gastric Carcinoma
V Zolota, V Tzelepi, A Liava, P Tsiamalos, K Vagenas, C Scopa, A Tsamandas. University of Patras School of Medicine, Patras, Greece
Background: p27Kip1 is a cell-cycle inhibitory protein and its downregulation is mediated by its specific ubiqitin subunit Skp2. PTEN is a tumor suppressor gene which upregulates p27. This study investigates p27, Skp2 and PTEN expression in gastric carcinoma (GC).
Design: The study included 127 patients with GC who underwent gastrectomy. None of the patients received any chemotherapy or radiotherapy prior to, or after surgery. Eight tumors were TNM-stage I, 39 II, 61 III, and 19 IV, whereas 95 tumors were low-grade (grade I and II intestinal type adenocarcinomas) and 32 high-grade (grade III intestinal type, and diffuse type adenocarcinomas). Formally fixed, paraffin- embedded 4m sections were subjected to immunohistochemistry using monoclonal antibodies for p27, Skp2 and PTEN. Nuclear staining was considered as positive. Results were correlated with pathologic data and patients' survival. Mean follow-up time was 45.3 months (range 3.5-140 months).
Results: Expression of p27, Skp2 and PTEN was recorded in 78/127 (61.4%), 57/127 (44.8%) and 99/127 (77.9%), respectively. PTEN and p27 expression was higher and Skp2 expression was lower in tumors of early stage and low grade compared to those of advanced stage and high grade. Skp2 expression levels were inversely correlated to p27 and PTEN in gastric carcinomas (p=0.0039 and p=0.0068 respectively). Statistical analysis revealed a positive correlation between PTEN expression and survival (p=0.007); Skp2 expression was negatively associated with survival (p=0.015). Cox regression analysis revealed that tumor grade and stage, and PTEN expression were independent prognostic factors (CI: 0.032-0.502, p=0.03, CI:1.167-5.408, p=0.019, CI: 1.065-41.082, p=0.032, respectively).
Conclusions: The study demonstrates that in GC loss of PTEN and p27 expression and enhancement of Skp2 expression are associated with adverse pathological parameters and increased risk for tumor recurrence. Loss of p27 in gastric carcinomas may be mediated by Skp2 overexpression. PTEN is possibly involved in the regulation of p27 levels via negative regulation of Skp2.
PTEN, p27 and Skp2 expressiona, d, f:p<0.001, b: p=0.0029, c:p=0.0012, e: p=0.031
|Low grade GC||87.311.9a||79.213.2c||22.416.3e|
|High grade GC||7.42.5a||5.33.1c||38.855.63e|
|TNM stages I+II||86.18.34b||73.17.32d||22.786.92f|
|TNM stages III+IV||12.41.2b||5.22.7d||53.017.34f|
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 105, Tuesday Afternoon