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Cancer. 2010 Nov 15;116(22):5179-87. doi: 10.1002/cncr.25481.

Expression of p16(INK4A) but not hypoxia markers or poly adenosine diphosphate-ribose polymerase is associated with improved survival in patients with pancreatic adenocarcinoma.

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  • 1Department of Radiation Oncology, Stanford University, Stanford, CA, USA. dtchang@stanford.edu

Abstract

BACKGROUND:

Pancreatic cancer is associated with mutations in the tumor suppressor gene cyclin-dependent kinase inhibitor 2A (p16(INK4A) ), a regulator of the cell cycle and apoptosis. This study investigates whether immunohistochemical expression of p16(INK4A) as well as hypoxia markers and poly adenosine diphosphate-ribose polymerase (PARP) correlates with survival in patients with resected pancreatic adenocarcinoma.

METHODS:

Seventy-three patients with pancreatic adenocarcinoma who underwent curative resection at Stanford University were included. From the surgical specimens, a tissue microarray was constructed using triplicate tissue cores from the primary tumor and used for immunohistochemical staining for the following markers: carbonic anhydrase IX, dihydrofolate reductase, p16(INK4A) , and PARP1/2. Staining was scored as either positive or negative and percentage positive staining. Staining score was correlated with overall survival (OS) and progression-free survival (PFS).

RESULTS:

Of the markers tested, only immunohistochemical expression of p16(INK4A) correlated with clinical outcome. On univariate analysis, p16(INK4A) expression in the tumor was associated with improved OS (P = .038) but not PFS (P = .28). The median survival for patients with positive versus negative p16(INK4A) staining was 28.8 months versus 18 months. On multivariate analysis, p16(INK4A) expression was associated with improved OS (P = .026) but not PFS (P = .25). Age (P = .0019) and number of nodes involved (P = .025) were also significant for OS. Adjuvant chemotherapy and margin status did not correlate with OS or PFS.

CONCLUSIONS:

Expression of p16(INK4A) is associated with improved OS in patients with resected pancreatic adenocarcinoma. Further investigation is needed for validation, given conflicting data in the published literature. .

PMID:
20665497
DOI:
10.1002/cncr.25481
[PubMed - indexed for MEDLINE]
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