Angiogenesis: A prognostic determinant in pancreatic cancer?

Zee, Jill A. van der; Eijck, Casper H.J. van; Hop, Wim C. J.; Dekken, Herman van; Dicheva, Bilyana M.; Seynhaeve, Ann L.B.; Koning, Gerben A.; Eggermont, Alexander M.M.; Hagen, Timo L.M. ten

doi:10.1016/j.ejca.2011.08.016

Cited by 33 publications

(33 citation statements)

References 60 publications

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“…This intriguing finding could, in part, explain the discrepancy in reports on the prognostic role of vessel density. Indeed, some groups have described a strong prognostic impact, while other reports have failed to identify a correlation of vessel density with survival [27–30, 38]. Of note, angiogenesis inhibitors failed to demonstrate efficacy in PDAC [4].…”

Section: Discussionmentioning

confidence: 99%

“…Depletion or „re-education“ of the stroma can, in certain conditions, lead to increased vessel density and increased intratumoral gemcitabine concentration, enhancing therapeutic response [13, 20–22], albeit stromal alteration can have mixed effects on tumor progression [23–26]. Also, the accuracy of vessel density assessment in PDAC has been hampered by the examination of small tumor regions, and mixed findings have been reported regarding the prognostic value of vascularity [27–30]. Importantly, previous clinical analyses failed to examine hypoxia and vessel density in the context of desmoplastic stroma [25, 26, 31–33].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…Consequently, angiogenesis quantified by microvessel density (CD31 staining) seems to be more prominent in NPPC than in PDAC. 33 Another protein, the transcription factor ''high-mobility group A1,'' is expressed at higher levels in PDAC than in NPPC. Interestingly it is associated with poor survival when present in NPPC.…”

Section: Proteins Growth Factors and Receptorsmentioning

confidence: 99%

Histological and Molecular Subclassification of Pancreatic and Nonpancreatic Periampullary Cancers: Implications for (Neo) Adjuvant Systemic Treatment

et al. 2014

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The benefit of adjuvant chemotherapy for resected pancreatic ductal adenocarcinoma (PDAC) has been confirmed in randomized controlled trials. For nonpancreatic periampullary cancers (NPPC) originating from the distal bile duct, duodenum, ampulla, or papilla of Vater, the role of adjuvant therapy remains largely unclear. This review describes methods for distinguishing PDAC from NPPC by means of readily available and recently developed molecular diagnostic methods. The difficulties of reliably determining the exact origin of these cancers pathologically also is discussed. The review also considers the possibility of unintentional inclusion of NPPC in the most important adjuvant trials on PDAC and the subsequent implications for interpretation of the results. The authors conclude that correct determination of the origin of periampullary cancers is essential for clinical management and should therefore be systematically incorporated into clinical practice and future studies.

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“…The median survival rate is 6 months or less, and the five-year survival rate for PDAC is only about 5%. A majority of patients present late, with locally advanced disease or with cancer already metastasized to distant organs and thus they are precluded from a resection2. In a minority of patients, occasionally a curative resection is successful, however their prognosis remains poor, with the median survival rate after surgery of 11–20 months3.…”

mentioning

confidence: 99%

“…Despite conflicting views about the formation and recruitment of new blood vessels in human PDAC24567, decades of studies demonstrate that PDAC, like other cancers, needs new and destabilized blood vessels (tumor angiogenesis) as a prerequisite event for the growth and progression as well as dissemination of tumor cells for metastasis78. Thus, targeting these blood vessels to prevent tumor growth and metastasis may provide novel strategies for PDAC therapy891011.…”

mentioning

confidence: 99%

Pancreatic Tumor Cell Secreted CCN1/Cyr61 Promotes Endothelial cell migration and Aberrant Neovascularization

Maity

Mehta

Haque

et al. 2014

Sci Rep

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The complex signaling networks between cancer cells and adjacent endothelial cells make it challenging to unravel how cancer cells send extracellular messages to promote aberrant vascularization or tumor angiogenesis. Here, in vitro and in vivo models show that pancreatic cancer cell generated unique microenvironments can underlie endothelial cell migration and tumor angiogenesis. Mechanistically, we find that pancreatic cancer cell secreted CCN1/Cyr61 matricellular protein rewires the microenvironment to promote endothelial cell migration and tumor angiogenesis. This event can be overcome by Sonic Hedgehog (SHh) antibody treatment. Collectively, these studies identify a novel CCN1 signaling program in pancreatic cancer cells which activates SHh through autocrine-paracrine circuits to promote endothelial cell migration and tumor angiogenesis and suggests that CCN1 signaling of pancreatic cancer cells is vital for the regulation of tumor angiogenesis. Thus CCN1 signaling could be an ideal target for tumor vascular disruption in pancreatic cancer.

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Angiogenesis: A prognostic determinant in pancreatic cancer?

Cited by 33 publications

References 60 publications

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

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

Histological and Molecular Subclassification of Pancreatic and Nonpancreatic Periampullary Cancers: Implications for (Neo) Adjuvant Systemic Treatment

Pancreatic Tumor Cell Secreted CCN1/Cyr61 Promotes Endothelial cell migration and Aberrant Neovascularization

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