Z Gastroenterol 2018; 56(08): e324-e325
DOI: 10.1055/s-0038-1668984
Kurzvorträge
Gastroenterologische Onkologie
Pankreaskarzinom: Neurale Infiltration, Fernmetastasierung, Prognose – Freitag, 14. September 2018, 08:15 – 09:19, 22b
Georg Thieme Verlag KG Stuttgart · New York

Increased Cathepsin D expression has a negative prognostic effect on survival in gemcitabine treated patients with pancreatic ductal adenocarcinoma

UM Mahajan
1   Klinikum der LMU München-Grosshadern, Medizinische Klinik und Poliklinik II, München, Deutschland
,
E Goni
1   Klinikum der LMU München-Grosshadern, Medizinische Klinik und Poliklinik II, München, Deutschland
,
E Langhoff
2   Universitätsmedizin Greifswald, Greifswald, Deutschland
,
S Kruger
3   Klinikum der LMU München-Grosshadern, Medizinische Klinik und Poliklinik III, München, Deutschland
,
S Ormanns
4   Klinikum der LMU München-Grosshadern, Pathologische Institut, München, Deutschland
,
G Beyer
1   Klinikum der LMU München-Grosshadern, Medizinische Klinik und Poliklinik II, München, Deutschland
,
FU Weiss
2   Universitätsmedizin Greifswald, Greifswald, Deutschland
,
T Kirchner
4   Klinikum der LMU München-Grosshadern, Pathologische Institut, München, Deutschland
,
J Werner
5   Klinikum der LMU München-Grosshadern, Klinik für Allgemein-, Viszeral-, Gefäß- und Transplantationschirurgie, München, Deutschland
,
J D'haese
5   Klinikum der LMU München-Grosshadern, Klinik für Allgemein-, Viszeral-, Gefäß- und Transplantationschirurgie, München, Deutschland
,
M von Bergwelt
3   Klinikum der LMU München-Grosshadern, Medizinische Klinik und Poliklinik III, München, Deutschland
,
V Heinemann
3   Klinikum der LMU München-Grosshadern, Medizinische Klinik und Poliklinik III, München, Deutschland
,
MM Lerch
2   Universitätsmedizin Greifswald, Greifswald, Deutschland
,
S Böck
3   Klinikum der LMU München-Grosshadern, Medizinische Klinik und Poliklinik III, München, Deutschland
,
J Mayerle
1   Klinikum der LMU München-Grosshadern, Medizinische Klinik und Poliklinik II, München, Deutschland
› Author Affiliations
Further Information

Publication History

Publication Date:
13 August 2018 (online)

 
 

    Background:

    The lysosomal aspartic protease Cathepsin D (CatD) is overexpressed and hypersecreted in many cancers and hereby influences cell death. Previously, in the ESPAC-3 cohort we determined a significantly increased median overall survival in cathepsin D low expressing PDAC patients. Gemcitabine treatment was significantly less effective in patients with high CatD expression compared to 5FU treated patients. Here, we present a prospective validation study.

    Methods:

    Sample size calculation based on the c2LR, 1DF [3.58] from our previous study warranted 76 gemcitabine treated patients asking for a power of 0.8 and p < 0.05. Tumor tissue microarrays of 79 patients from the „informative patients” with PDAC receiving adjuvant gemcitabine treatment recruited at a single center were stained with anti-CatD (C-20) antibody. Patients were dichotomously distributed in lower and higher H-scores (H-score cut-off: 22.35) for generating Kaplan-Meier curves and to perform log-rank testing and Cox proportional hazards models. All statistical tests were two-sided.

    Results:

    In our independent validation cohort with 228 cores from 79 patients (96.8%) median overall survival of patients was reported with 30.57 months (95%CI, 23.24 – 37.41). Median survival for patients for low CatD expression in the validation cohort was 48.92 (95%CI, 20.97 – 55.34) months vs. 25.08 (95%CI, 18.69 – 34.19) months for high CatD expression, c2 LR,1DF= 5.40; P = 0.02 confirming our null hypothesis. Multivariate analysis with sex, lymph node status, local invasion status and Cathepsin D expression revealed CatD expression as independent predictive marker in gemcitabine treated patients with a hazard ratio of 2.25 (95% CI, 1.03 – 4.94, p = 0.04).

    Conclusions:

    Subject to prospective validation within a randomized trial, gemcitabine is less effective for patients with high CatD expression and could serve as a stratification marker for biomarker driven pancreatic cancer therapy.


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