1642P - Prognostic impact of an immunomorphological signature integrating immune, fibroblastic and tumor markers in a series of 217 resected pancreatic adenocarcinoma patients

Background

Pancreatic ductal adenocarcinoma (PDAC) is marked by a desmoplastic stroma and poor prognosis. Current pathological or molecular classifications are discordant and not applied in routine clinical practice. In order to predict relapse-free survival (RFS), we aimed to develop an immunohistochemical (IHC) signature involving immune, fibroblastic, tumor markers in a cohort of 217 resected PDAC patients.

Methods

Tumors were collected for tissue microarrays construction and characterized by digital pathology with 13 IHC stains at the tumor epithelial, immune and stromal compartments. Cox proportional hazard models were performed to estimate hazard ratio and CI95% for factors associated with RFS.

Results

Multivariate Cox analysis showed that loss of membrane localization of β-catenin on tumor cells (HR=1.54, 95%CI=1.08-2.20, p=0.02), a low density of tumor infiltrating CD8+ T-cells (HR=1.72, 95%CI =1.23-2.41, p<0.01) and a high percentage of HSP47-positive Cancer-Associated Fibroblasts (CAF) (HR=1.41, 95%CI =1.03-1.96, p=0.03) were independent predictors of reduced RFS. Based on the expression of these three markers, we constructed a scoring system to classify resected PDAC into three distinct prognostic groups (p<0.001): 0/1+ (mRFS=8.4, 95%CI=6.7-9.9), 2+ (mRFS=13.1, 95%CI=10.7-16.4) and 3+ (mRFS=22.5, 95%CI=17.1-131.7). The discriminative ability of the three-group model was confirmed in overall survival analysis. Furthermore, with the exception of neoadjuvant therapy (p=0.03) and the presence of lymphovascular invasions (p=0.04), the score developed was not related to other clinicopathological data.

Conclusions

We propose a novel RFS prediction model based on three independent prognostic IHC markers evaluating tumor epithelial, immune and fibroblastic compartments. These results highlight considerable heterogeneity in the survival of patients with resected PDAC. Moreover, this is the first demonstration of the prognostic character of HSP47 by IHC in PDAC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.