Prognostic role and correlation of CA9, CD31, CD68 and CD20 with the desmoplastic stroma in pancreatic ductal adenocarcinoma

We assessed the prognostic value of hypoxia (carbonic anhydrase 9; CA9), vessel density (CD31), with macrophages (CD68) and B cells (CD20) that can interact and lead to immune suppression and disease progression using sc
We assessed the prognostic value of hypoxia (carbonic anhydrase 9; CA9), vessel density (CD31), with macrophages (CD68) and B cells (CD20) that can interact and lead to immune suppression and disease progression using scanning and histological mapping of whole-mount FFPE pancreatectomy tissue sections from 141 primarily resectable pancreatic ductal adenocarcinoma (PDAC) samples treated with surgery and adjuvant chemotherapy. Their expression was correlated with clinicopathological characteristics, and overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), also in the context of stroma density (haematoxylin-eosin) and activity (alpha-smooth muscle actin). The median OS was 21 months after a mean follow-up of 20 months (range, 2–69 months). The median tumor surface area positive for CA9 and CD31 was 7.8% and 8.1%, respectively. Although total expression of these markers lacked prognostic value in the entire cohort, nevertheless, high tumor compartment CD68 expression correlated with worse PFS (p = 0.033) and DMFS (p = 0.047). Also, high CD31 expression predicted for worse OS (p = 0.004), PFS (p = 0.008), LPFS (p = 0.014) and DMFS (p = 0.004) in patients with moderate density stroma. High stromal and peripheral compartment CD68 expression predicted for significantly worse outcome in patients with loose and moderate stroma density, respectively. Altogether, in contrast to the current notion, hypoxia levels in PDAC appear to be comparable to other malignancies. CD31 and CD68 constitute prognostic markers in patient subgroups that vary according to tumor compartment and stromal density. Our study provides important insight on the pathophysiology of PDAC and should be exploited for future treatments.
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Metadaten
Author:Angela Diana, Lai Mun Wang, Zenobia D’Costa, Abul Azad, Michael A. Silva, Zahir Soonawalla, Paul Allen, Stanley Liu, W. Gillies McKenna, Ruth J. Muschel, Emmanouil Fokas
URN:urn:nbn:de:hebis:30:3-458204
DOI:http://dx.doi.org/10.18632/oncotarget.12022
ISSN:1949-2553
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=27637082
Parent Title (English):OncoTarget
Publisher:Impact Journals LLC
Place of publication:[s. l.]
Document Type:Article
Language:English
Year of Completion:2016
Date of first Publication:2016/09/14
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/03/08
Tag:desmoplastic stroma; hypoxia; macrophages; prognosis; vessel density
Volume:7
Issue:45
Pagenumber:14
First Page:72819
Last Page:72832
Note:
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
HeBIS PPN:43210836X
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0

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