P53 overexpression and Ki67-index are associated with outcome in ductal pancreatic adenocarcinoma with adjuvant gemcitabine treatment
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P53 overexpression and Ki67-index are associated with outcome in ductal pancreatic adenocarcinoma with adjuvant gemcitabine treatment. / Striefler, Jana K; Sinn, Marianne; Pelzer, Uwe; Jühling, Anja; Wislocka, Lilianna; Bahra, Marcus; Sinn, Bruno V; Denkert, Carsten; Dörken, Bernd; Oettle, Helmut; Riess, Hanno; Bläker, Hendrik; Lohneis, Philipp.
In: PATHOL RES PRACT, Vol. 212, No. 8, 08.2016, p. 726-34.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - P53 overexpression and Ki67-index are associated with outcome in ductal pancreatic adenocarcinoma with adjuvant gemcitabine treatment
AU - Striefler, Jana K
AU - Sinn, Marianne
AU - Pelzer, Uwe
AU - Jühling, Anja
AU - Wislocka, Lilianna
AU - Bahra, Marcus
AU - Sinn, Bruno V
AU - Denkert, Carsten
AU - Dörken, Bernd
AU - Oettle, Helmut
AU - Riess, Hanno
AU - Bläker, Hendrik
AU - Lohneis, Philipp
N1 - Copyright © 2016 Elsevier GmbH. All rights reserved.
PY - 2016/8
Y1 - 2016/8
N2 - 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.
AB - 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.
KW - Aged
KW - Antimetabolites, Antineoplastic/therapeutic use
KW - Carcinoma, Pancreatic Ductal/drug therapy
KW - Chemotherapy, Adjuvant
KW - Cyclin-Dependent Kinase Inhibitor p16/metabolism
KW - Deoxycytidine/analogs & derivatives
KW - Disease-Free Survival
KW - Female
KW - Humans
KW - Immunohistochemistry
KW - Ki-67 Antigen/metabolism
KW - Male
KW - Middle Aged
KW - Neoplasm Staging
KW - Pancreatic Neoplasms/drug therapy
KW - Prognosis
KW - Survival Rate
KW - Treatment Outcome
KW - Tumor Suppressor Protein p53/metabolism
KW - Up-Regulation
U2 - 10.1016/j.prp.2016.06.001
DO - 10.1016/j.prp.2016.06.001
M3 - SCORING: Journal article
C2 - 27461834
VL - 212
SP - 726
EP - 734
JO - PATHOL RES PRACT
JF - PATHOL RES PRACT
SN - 0344-0338
IS - 8
ER -