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Pathol Res Pract. 2016 Aug;212(8):726-34. doi: 10.1016/j.prp.2016.06.001. Epub 2016 Jun 8.

P53 overexpression and Ki67-index are associated with outcome in ductal pancreatic adenocarcinoma with adjuvant gemcitabine treatment.

Author information

1
Charité - Universitätsmedizin Berlin, Department of Medical Oncology and Haematology, Augustenburger Platz 1, 13353 Berlin, Germany.
2
Charité - Universitätsmedizin Berlin, Department of General, Visceral and Transplantation Surgery, Augustenburger Platz 1, 13353 Berlin, Germany.
3
Charité - Universitätsmedizin Berlin, Institute of Pathology, Charitéplatz 1, 10117 Berlin, Germany.
4
Outpatient Department Hematology/Oncology, Friedrichstrasse 53, 88045 Friedrichshafen, Germany.
5
Charité - Universitätsmedizin Berlin, Institute of Pathology, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: philipp.lohneis@charite.de.

Abstract

In pancreatic cancer there is a need for prognostic risk stratification and subsequent therapy strategies. Molecular analysis has shown in different cancers that variation in clinical behavior can be associated with specific alterations. The cell cycle regulators p16 and p53 belong to the most often alterated genes in pancreatic ductal adenocarcinoma (PDAC). We analyzed protein expression of p16, p53 and Ki67 by immunohistochemistry in 162 tumours of the CONKO-001 trial that investigated the role of adjuvant gemcitabine in pancreatic cancer patients. We could show that high proliferation of tumours and strong and consistent nuclear p53 expression by tumour cells is associated with a worse disease-free survival and overall survival in the overall study population. However, stratified analysis according to treatment arm revealed that the effect of deregulated p53 expression and high Ki67 expression was restricted to the disease free survival of patients treated with adjuvant gemcitabine. In multivariable survival analysis, p53 did not retain its prognostic status. Our study supports the important role of p53 and Ki67 expression in PDAC. They provide prognostic information in patients with adjuvant gemcitabine treatment and may contribute to treatment decision. However, these results should be validated in further studies.

KEYWORDS:

carcinoma; gemcitabine; ki67; p16; p53; pancreas

PMID:
27461834
DOI:
10.1016/j.prp.2016.06.001
[Indexed for MEDLINE]

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