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Prognostic value of p27 kip1 expression in adenocarcinoma of the pancreatic head region.

BACKGROUND
p27(kip1) is a tumour suppressor gene, functioning as a cyclin-dependent kinase inhibitor, and an independent prognostic factor in breast, colon, and prostate adenocarcinomas. Conflicting data are reported for adenocarcinoma of the pancreas. The aim of this study was to establish the prognostic value of p27(kip1) expression in adenocarcinoma of the pancreatic head region.


PATIENTS AND METHODS
The study included 45 patients (male/female ratio 2:1; mean age 59, range 38-82 years) with adenocarcinomas of the pancreatic head region: 24 - pancreatic head, 18 - periampullary and 3 - uncinate process. The patients underwent the Kausch-Whipple pancreatoduodenectomy (n=39), pylorus-preserving pancreatoduodenectomy (n=5), or nearly total pancreatectomy (n=1). Eight patients received adjuvant chemotherapy postoperatively. Follow-up time ranged from 3 to 60 months. Tumours were staged according to the pTNM classification (UICC 1997). Immunohistochemistry was done on paraffin-embedded blocks from tumour sections. Quantitative determination of p27(kip1) expression was based on the proportion of p27(kip1) -positive cells (< 5% = negative). Survival analysis was carried out using the Kaplan-Meier method and Cox regression model.


RESULTS
Positive p27(kip1) expression was detected in 22 tumours (49%), whereas 23 tumours (51%) were p27(kip1)-negative. There were no significant correlations between p27(kip1) index and stage or lymph node involvement. Median survival time in patients with p27(kip1)-positive tumours was 19 months, whereas in patients with p27(kip1)-negative tumours it was 18 months (p=0.53). A significant relationship was found between p27(kip1)-negative tumours and radical resection (p=0.04). Multivariate survival analysis revealed that the localization of the tumour (pancreatic head/uncinate process vs periampullary) was the only significant and independent prognosticator (p = 0.01, Cox regression model). Resection margins involvement and grade remained nearly significant prognostic factors (p=0.07 and p=0.09, respectively).


CONCLUSION
We conclude that p27(kip1) has limited overall prognostic utility in resected carcinoma of the pancreatic head region, but its potential role as a marker of residual disease needs to be further assessed.