The prognostic role of desmoplastic stroma in pancreatic ductal adenocarcinoma
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Lai Mun Wang1,*, Michael A. Silva2,*, Zenobia D’Costa3,*, Robin Bockelmann3,*, Zahir Soonawalla2, Stanley Liu4, Eric O’Neill3, Somnath Mukherjee3, W. Gillies McKenna3, Ruth Muschel3, Emmanouil Fokas3
1Department of Pathology, Oxford University Hospital NHS Trust, University of Oxford, Oxford, UK
2Department of Surgery, Oxford University Hospital NHS Trust, Oxford, UK
3Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, Oxford, UK
4Department of Radiation Oncology, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada
*These authors contributed equally to this work
Emmanouil Fokas, e-mail: [email protected]
Keywords: desmoplasia, stroma density, αSMA, pancreatic cancer, prognosis
Received: September 21, 2015 Accepted: December 01, 2015 Published: December 26, 2015
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.
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