The prognostic value of stroma in pancreatic cancer in patients receiving adjuvant therapy

Abstract

Background: Pancreatic ductal adenocarcinoma (PDA) is comprised of a prominent desmoplastic stromal compartment and only 10-40% of the tumour consists of PDA cells. However, how stromal components should be assessed and how the characteristics of the stromal compartment determine clinical outcomes in PDA patients remain unknown.

Method: A cohort of 66 consecutive patients who underwent pancreaticoduodenectomy and were primarily followed at Johns Hopkins Hospital between 1998 and 2004, and treated with adjuvant therapy, were included in a retrospective analysis. Resected PDA blocks with good tissue preservation were available for all patients. A new, computer-aided, quantitative method was developed to assess the density and activity of stroma in PDAs and the associations of these characteristics with clinical outcomes.

Results: High stromal density in resected PDA was found to be significantly associated with longer disease-free [adjusted hazard ratio (aHR) 0.39; P = 0.001] and overall (aHR 0.44; P = 0.004) survival after adjusting for the use of pancreatic cancer vaccine therapy, as well as gender and resection margin positivity. Stromal activity, representing activated pancreatic stellate cells in PDAs, was not significantly associated with the prognosis of resected PDAs.

Conclusions: These results illustrate the complexity of the role of stroma in PDAs. Further exploration of the prognostic ability of the characteristics of stroma is warranted.

Figure 1

Immunohistochemistry staining and quantification of stromal density and activity in pancreatic ductal adenocarcinoma (PDA). (a) Representative immunohistochemistry staining of pankeratin (brown signals) and collagens (blue signals). (b) Representative quantification of stromal density in the intratumoral area (enclosed). (c) Representative immunohistochemistry staining of smooth muscle actin (SMA) (brown signals). (d) Representative quantification of stromal activity in the intratumoral area (enclosed). (e) Representative PDA with high stromal activity/strong SMA expression. (f) Representative PDA with low stromal activity/weak SMA expression

Figure 2

Kaplan–Meier estimates of (a) overall and (b) disease-free survival in individuals with high stromal density (≥0.8, light blue) and low stromal density (<0.8, dark blue) over the first 60 months of follow-up. Numbers of individuals at risk in each stromal density category are shown below the graphs