2. Department of Surgery, Riga Stradins University, Dzirciema Street 16, Riga, Latvia.
Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumours with dismal prognosis. Although curative resection with adjuvant chemoradiotherapy is the most effective treatment, the surgery is frequently limited by cancer spread or poor general status of the patient. Relatively few studies have analysed the outcomes of surgically treated pancreatic cancer. Controversies exist about several biological markers that could be important in the era of personalized medicine. Thus, the aim of our study was to determine frequency and extent of expression of biological markers (Ki-67, p53, Bcl-2, vimentin, CD44) in relation to survival after potentially curative radical surgical treatment of PDAC.
Methods: The study was designed as retrospective, protocol-based evaluation of 63 consecutive pancreatic ductal adenocarcinoma cases. Ki-67, p53, Bcl-2, vimentin and CD44 expression was evaluated by immunohistochemistry. The survival was assessed by Kaplan-Meier method. Spearman's rank correlation, t-test and Kruskal-Wallis test, log-rank and Cox regression analysis were used for appropriate statistical analysis. The study was approved by Committee of Ethics.
Results: Patients' mean age was 63.2 years. The mean survival was 19.5 month (95% confidence interval (CI) = 11.3-27.8). The tumours were mostly T3-4 (95.2%; 95% CI = 86.7-98.2) and larger than 2 cm (90.9%; 95% CI = 78.8-96.3). Metastases in lymph nodes were identified in 67.2% (95% CI = 54.7-77.7) cases. The most frequent tumour stage was IIB (62.3%; 95% CI = 49.7-73.4). Resection margins were involved in 51.7% (95% CI = 39.1-64.1) cases. Perineural and intraneural invasion was found in 84.1% (95% CI = 73.1-91.1) of patients. Correlation was found between survival and high histologic grade (p = 0.017), resection margin involvement (p = 0.039), high Ki-67 (p = 0.022) and vimentin positivity (p = 0.023), as well as between CD44 expression and N stage (p = 0.022) and Ki-67 (p = 0.010). There was a trend to correlation between CD44 and vimentin expression (p = 0.058) as well as between p53 expression and peri- and intraneural invasion (p = 0.053).
Conclusions: The survival after surgical resection of pancreatic carcinoma remains poor. The tumour grade, positive resection margins, proliferation fraction and epithelial-mesenchymal transition affect patients' survival. CD44 expression correlates with Ki-67 and N stage. Trend to correlation was observed between p53 expression and peri- and intraneural growth.
Keywords: pancreatic cancer, survival, immunohistochemistry, CD44, Ki-67, vimentin, p53