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

Autor: Bernd Dörken, Hendrik Bläker, Philipp Lohneis, Marcus Bahra, Hanno Riess, Marianne Sinn, Anja Jühling, Bruno Valentin Sinn, Helmut Oettle, Uwe Pelzer, Carsten Denkert, Lilianna Wislocka, Jana K. Striefler
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Oncology
Antimetabolites
Antineoplastic
medicine.medical_specialty
medicine.medical_treatment
Deoxycytidine
Disease-Free Survival
Pathology and Forensic Medicine
03 medical and health sciences
0302 clinical medicine
Pancreatic cancer
Internal medicine
medicine
Carcinoma
Humans
Cyclin-Dependent Kinase Inhibitor p16
Survival analysis
Aged
Neoplasm Staging
business.industry
Cell Biology
Middle Aged
Cell cycle
Prognosis
medicine.disease
Immunohistochemistry
Gemcitabine
Up-Regulation
Pancreatic Neoplasms
Survival Rate
Ki-67 Antigen
Treatment Outcome
030104 developmental biology
medicine.anatomical_structure
Chemotherapy
Adjuvant
030220 oncology & carcinogenesis
Adenocarcinoma
Female
Tumor Suppressor Protein p53
Pancreas
business
Adjuvant
Carcinoma
Pancreatic Ductal
medicine.drug
Zdroj: Pathology - Research and Practice. 212:726-734
ISSN: 0344-0338
DOI: 10.1016/j.prp.2016.06.001
Popis: 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.
Databáze: OpenAIRE
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