Abstract 1493: Analysis of fibrosis and stromal components in metastatic pancreatic cancer (PC) autopsy specimens
Authors: Shroff Rachna T. , Morris Jeffrey , Nogueras-Gonzalez Graciela M. , Anderson Judy M. , Hollingsworth Michael A. , Abbruzzese James L. , Wang Huamin M. 
Published: August 2012

Abstract
Background: PC remains a deadly malignancy with a paucity of effective therapeutic options. Recent data generated in a genetically engineered mouse model of PC suggests that the notorious chemoresistance of this disease is due to dense fibrosis and stromal proliferation that precludes effective drug delivery to the cancer cells. However clinical experience in patients with metastatic disease suggests that metastatic sites may respond differently from the pancreatic primary (PP). Such variability could be related to differences in the tumor-stroma relationship between the PP and metastatic sites. We used paired specimens from the University of Nebraska Medical Center's rapid autopsy program (RAP) to assess histologic markers of fibrosis and stromal proliferation between the PP and metastatic sites to better characterize these differences. Methods: The RAP has been previously described (Stratford et al. PLoS Med 2010). We identified 12 matched specimens that included PP tissue in addition to metastatic lesions from liver, lung, abdominal cavity, or other sites. Slides were stained with hematoxylin and eosin (to assess for % fibrosis) and vimentin, CD10, and CD68 (stromal markers) and scored based on pathologic review (HMW). Percent fibrosis was a composite measure based on stromal components, including collagen, fibroblasts, and inflammatory cells. Mixed linear model methods with repeated measures were used to determine whether there was a difference in % fibrosis and CD68 between patients’ tumors. Generalized estimating equations were used to determine whether there was a difference in vimentin and CD10 between patients’ tumors. Bonferroni adjusted p-value=0.0125 (α=0.05 / 4 tests) was used as significant alpha level for the tests. Statistical analysis was performed using SAS version 9.2 and STATA/SE version 11.2 software. Results: Percent fibrosis was statistically different between PP tissue and all metastatic sites (p=0.002) with metastatic lesions demonstrating less fibrosis than the respective paired PP. There were no statistically significant differences in CD10, CD68 or vimentin staining between the PP and metastatic sites; however liver metastases did trend towards significantly more stromal cellular proliferation, based on CD10, vimentin, and CD68 staining, when compared to other metastatic sites. Conclusions: There was less stromal deposition and fibrosis in metastatic sites versus the PP's that were examined. This difference could play a role in the chemosensitivity of the primary tumor compared to metastatic sites of disease. Furthermore, the liver appears to have more striking stromal cellular proliferation compared to other metastatic sites, which could also affect drug penetration and outcome. These differences in the tumor-stroma relationship should be further validated and interventions evaluated to improve drug delivery to the PP and metastatic sites in PC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1493. doi:1538-7445.AM2012-1493