Original article—liver, pancreas and biliary tractThe Activated Stroma Index Is a Novel and Independent Prognostic Marker in Pancreatic Ductal Adenocarcinoma
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Clinical Data and Pancreatic Tissue Collection
Demographic, surgical, and pathologic data from a prospectively registered data base were analyzed retrospectively. Tissue collection and preservation were performed as described previously.14 The use of human material for analysis was approved by the ethics committee of the University of Heidelberg in Germany. Written informed consent was obtained from all patients.
Immunohistochemical Analysis and Computer-Assisted Image Analysis
Paraffin-embedded tissue blocks of 300 pathologically confirmed PDAC patients undergoing surgery between January 2002 and November
Peritumoral Activation of Pancreatic Stellate Cells and Deposition of Collagen
Four major patterns of collagen deposition were observed with regard to PSC activity (α-SMA expression). In chronic pancreatitis-like changes of the peritumoral stroma, interlobar septa were broadened where strong α-SMA staining colocalized with strong collagen staining (Figure 1A, B, D, and E). On the invasive front of the activated stroma, prominent α-SMA staining was visible in the periacinar spaces where collagen had not yet been deposited (Figure 1D and E, arrows). Within the cancerous
Discussion
The most important finding of the current study is the identification of the activity of the stromal component in PDAC as an independent prognostic marker in surgical cases.
At the genetic level, pancreatic cancer is a well-characterized neoplasm. By contrast, the molecular mechanisms linking the genetic changes to the aggressive nature of this disease remain poorly understood.17 One promising new development is the appreciation of the role of the cancer-associated stroma.18 Current evidence
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Supported in part by a Postdoctoral Research Program grant from the University of Heidelberg (C.W.M.). This work has been supported by EU Framework Programme 6, Integrated Project—Mol Diag-Pa Ca (Molecular Diagnosis of Pancreatic Cancer).
M.E., C.W.M., and S.R. contributed equally to this article.