The Potential Role of p27, Skp2, and PTEN Expression in Adenocarcinomas of the Ampulla of Vater and Pancreas (AAVP).
Nikolaos Katsiakis, John Maroulis, Vassiliki Zolota, Dionissios Karavias, Chrisoula Scopa, Athanassios Tsamandas. Patras University Medical School, 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 adenocarcinomas of the ampulla of Vater and pancreas (AAVP).
Design: The study included 64 patients with AAVP: group A 14 patients with adenocarcinoma of the ampulla, group B 23 patients with adenocarcinoma of the head of the pancreas and group C 7 patients with adenocarcinoma of the pancreas body. Patients of groups A and B underwent the Whipple procedure and patients of group C distal pancreatectomy. Eight tumors were TNM-stage I, 19 II, 27 III, and 10 IV, whereas 35 tumors were low-grade (high and moderately differentiated) and 29 high grade (poorly differentiated). Paraffin sections were subjected to immunohistochemistry using 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 8.3 months (range 3.5-18 months).
Results: Expression of p27, Skp2 and PTEN was recorded in 61.4% (39/64), 44.8% (28/64) and 77.9% (49/64), 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 AAVP (p=0.0042 and p=0.0059 respectively). Statistical analysis revealed a positive correlation between PTEN expression and survival (p=0.009); Skp2 expression was negatively associated with survival (p=0.013). 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).
|Low grade AAVP||87.3 ±11.9a||79.2 ±13.2c||22.41 ±6.3e|
|High grade AAVP||7.4± 2.5a||5.3 ±3.1c||38.85 ±5.63e|
|TNM stages I+II||86.1± 8.34b||73.1± 7.32d||22.78± 6.92f|
|TNM stages III+IV||12.4 ±1.2b||5.2 ±2.7d||53.01 ±7.34f|