title: Desmoplasia in Primary Tumors and Metastatic Lesions of Pancreatic Cancer.
abstract: OBJECTIVE
  Pancreatic ductal adenocarcinoma (PDAC) is characterized by high levels of fibrosis, termed desmoplasia, which is thought to hamper the efficacy of therapeutics treating PDAC. Our primary focus was to evaluate differences in the extent of desmoplasia in primary tumors and metastatic lesions. As metastatic burden is a primary cause for mortality in PDAC, the extent of desmoplasia in metastases may help to determine whether desmoplasia targeting therapeutics will benefit patients with late-stage, metastatic disease.
  
  
  METHODS
  We sought to assess desmoplasia in metastatic lesions of PDAC and compare it with that of primary tumors. Fifty-three patients' primaries and 57 patients' metastases were stained using IHC staining techniques.
  
  
  RESULTS
  We observed a significant negative correlation between patient survival and extracellular matrix deposition in primary tumors. Kaplan-Meier curves for collagen I showed median survival of 14.6 months in low collagen patients, and 6.4 months in high-level patients (log rank, P < 0.05). Low-level hyaluronan patients displayed median survival times of 24.3 months as compared with 9.3 months in high-level patients (log rank, P < 0.05). Our analysis also indicated that extracellular matrix components, such as collagen and hyaluronan, are found in high levels in both primary tumors and metastatic lesions. The difference in the level of desmoplasia between primary tumors and metastatic lesions was not statistically significant.
  
  
  CONCLUSIONS
  Our results suggest that both primary tumors and metastases of PDAC have highly fibrotic stroma. Thus, stromal targeting agents have the potential to benefit PDAC patients, even those with metastatic disease.
authors.affiliation: Clinical Translational Research Division, The Translational Genomics Research Institute, Phoenix, Arizona. cwhatcott@tgen.org hhan@tgen.org.
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Whatcott
authors.affiliation: Clinical Translational Research Division, The Translational Genomics Research Institute, Phoenix, Arizona.
authors.forename: Caroline H
authors.initials: CH
authors.lastname: Diep
authors.affiliation: Halozyme Therapeutics, San Diego, California.
authors.forename: Ping
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Integrated Cancer Genomics Division, The Translational Genomics Research Institute, Phoenix, Arizona.
authors.forename: Aprill
authors.initials: A
authors.lastname: Watanabe
authors.affiliation: Integrated Cancer Genomics Division, The Translational Genomics Research Institute, Phoenix, Arizona.
authors.forename: Janine
authors.initials: J
authors.lastname: LoBello
authors.affiliation: Computational Biology Division, The Translational Genomics Research Institute, Phoenix, Arizona.
authors.forename: Chao
authors.initials: C
authors.lastname: Sima
authors.affiliation: Laboratory of Analytical Pathology, The Van Andel Research Institute, Grand Rapids, Michigan.
authors.forename: Galen
authors.initials: G
authors.lastname: Hostetter
authors.affiliation: Halozyme Therapeutics, San Diego, California.
authors.forename: H Michael
authors.initials: HM
authors.lastname: Shepard
authors.affiliation: Clinical Translational Research Division, The Translational Genomics Research Institute, Phoenix, Arizona.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Von Hoff
authors.affiliation: Clinical Translational Research Division, The Translational Genomics Research Institute, Phoenix, Arizona. cwhatcott@tgen.org hhan@tgen.org.
authors.forename: Haiyong
authors.initials: H
authors.lastname: Han
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D024042:Collagen Type I / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D018572:Disease-Free Survival; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D024042:Collagen Type I; D024141:Collagen Type IV; D006820:Hyaluronic Acid