Prognostic Significance of Prognostic Significance of Cell Cycle Proteins p53, p21, p27, p14, and p16 in Adenocarcinomas of the Ampulla of Vater and Pancreas (AAVP).
Nikolaos Katsiakis, John Maroulis, Vassiliki Zolota, Dionissios Karavias, Chrisoula Scopa, Athanassios Tsamandas. University of Patras, Achaia, Greece
Background: This study investigates the immunohistochemical expression of 5 essential cell cycle proteins p53, p21, p27, p14 and p16 in AAVP and their correlation with classic pathologic tumor features, proliferating index (Ki67 positivity) and patients' survival.
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 pancreas head and group C 7 patients with adenocarcinoma of the pancreas body. Patients of groups A/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; 35 tumors were grade I and II and 29 grade III. Paraffin sections were subjected to immunohistochemistry with antibodies for p53, p21, p27, p14, p16, and Ki67. Nuclear staining was considered as positive. Mean follow-up time was 8.3 months (range 3.5-18 months).
Results: p53, p14, p16, p21 and p27 were detected in: 56%(35/64), 70%(44/64), 65%(41/64), 48%(30/64), and 82%(52/64) of the cases, respectively. Mean index for Ki67 was 29.4±48.2. High grade tumors exhibited higher indices for Ki67 (p=0.004), p53 (p=0.005) and p21 (p=0.024) compared to low grade tumors; p14 and p16 were more frequently present in low grade tumors (p<0.001 in both cases). Ki67, p53, p21 and p27 were more frequently expressed in advanced stage tumors (p=0.002, and p<0.001 in the later three cases). p14 and p16 were more frequently expressed in early stages (p<0.001 and p=0.012). Lower disease-free survival was correlated with high grade (p=0.0007), advanced stage (p=0.0008), and higher Ki67 index (p=0.0075). p53 expression was associated with lower disease-free survival only in high grade p21(+) tumors (p=0.021). Cox analysis revealed that tumor grade, stage, Ki67 and p53 index were independent prognostic factors (CI: 0.032-0.502, p=0.03, CI:1.167-5.408, p=0.019, CI: 1.006-1.057, p=0.016, CI:1.000-1.0044, p=0.028).
Conclusions: The study confirms that in cases of AAVP, tumor grade and stage and Ki67 and p53 indices are independent predictors of the outcome of the patients. p53 is associated with poor prognosis only in tumors overexpressing p21. Thus, high levels of p21 in tumor cells associated with aberrant p53 protein expression may result in tumor recurrence.
Category: Liver & Pancreas
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 204, Tuesday Afternoon