title: The prognostic role of desmoplastic stroma in pancreatic ductal adenocarcinoma.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant desmoplastic stroma. We examined the prognostic value of stroma density and activity in patients with resectable PDAC treated with surgery and adjuvant gemcitabine-based chemotherapy. FFPE-tissue from the pancreatectomy of 145 patients was immunohistochemically stained for haematoxylin-eosin and Masson's trichrome to assess stroma density, and alpha-smooth muscle actin (αSMA) expression for activated pancreatic stellate cells. Their expression was correlated with clinicopathological characteristics as well as overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS). After a mean follow-up of 20 months (range, 2-69 months), the median OS was 21 months and the 3-year OS was 35.7%. In multivariate analysis, highly-dense stroma was an independent prognostic parameter for OS (p = 0.001), PFS (p = 0.007), LPFS (p = 0.001) and DMFS (p = 0.002), while αSMA expression lacked significance. Interestingly, highly-dense stroma retained significance for the four clinical endpoints only in early (pT1-2) but not late (pT3-4) stage tumors. Additionally, late pT-stage (pT3-4), the presence of lymph node metastases (pN+ vs pN0), perineural/neural invasion and administration of adjuvant chemotherapy also correlated with prognosis in multivariate analysis. Altogether, stroma density constitutes an independent prognostic marker in PDAC patients treated with adjuvant chemotherapy. Our findings highlight the dynamic complexity of desmoplasia and indicate that highly-dense stroma is correlated with better outcome. Further validation of the prognostic value of stroma as a biomarker and its role in PDAC patients after adjuvant chemotherapy is warranted and will be performed in a prospective study.
authors.affiliation: Department of Pathology, Oxford University Hospital NHS Trust, University of Oxford, Oxford, UK.
authors.forename: Lai Mun
authors.initials: LM
authors.lastname: Wang
authors.affiliation: Department of Surgery, Oxford University Hospital NHS Trust, Oxford, UK.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Silva
authors.affiliation: Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, Oxford, UK.
authors.forename: Zenobia
authors.initials: Z
authors.lastname: D'Costa
authors.affiliation: Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, Oxford, UK.
authors.forename: Robin
authors.initials: R
authors.lastname: Bockelmann
authors.affiliation: Department of Surgery, Oxford University Hospital NHS Trust, Oxford, UK.
authors.forename: Zahir
authors.initials: Z
authors.lastname: Soonawalla
authors.affiliation: Department of Radiation Oncology, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
authors.forename: Stanley
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, Oxford, UK.
authors.forename: Eric
authors.initials: E
authors.lastname: O'Neill
authors.affiliation: Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, Oxford, UK.
authors.forename: Somnath
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, Oxford, UK.
authors.forename: W Gillies
authors.initials: WG
authors.lastname: McKenna
authors.affiliation: Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, Oxford, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Muschel
authors.affiliation: Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, Oxford, UK.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Fokas
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D021441:Carcinoma, Pancreatic Ductal / Q000556:secondary* / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010180:Pancreatectomy / Q000401:mortality*; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000628:therapy; D011379:Prognosis; D017154:Stromal Cells / Q000473:pathology*; D015996:Survival Rate
keywords: desmoplasia; pancreatic cancer; prognosis; stroma density; αSMA