title: alpha-Smooth Muscle Actin Expressing Stroma Promotes an Aggressive Tumor Biology in Pancreatic Ductal Adenocarcinoma.
abstract: OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is often characterized by a prominent desmoplastic stroma that is induced partially by alpha-smooth muscle actin (SMA)-expressing activated pancreatic stellate cells (PSCs). This study aimed to investigate the significance of alpha-SMA expression in PDAC and the correlation between alpha-SMA mRNA levels and the patient prognosis. METHODS: We obtained formalin-fixed, paraffin-embedded tissue samples from 109 patients with PDAC, who underwent pancreatectomy at our institution from 1992 to 2007. We measured alpha-SMA mRNA levels by quantitative real-time reverse transcription-polymerase chain reaction and investigated the association of alpha-SMA mRNA expression with clinicopathologic parameters and survival time. We also assessed the influence of activated PSCs on malignant behaviors of pancreatic cancer cells using in vitro experiments. RESULTS: alpha-SMA immunoreactivity was detected exclusively in the stroma of PDAC. The group with high alpha-SMA expression showed a significantly shorter survival, as shown by univariate analysis (P = 0.005) and multivariate analysis (P < 0.0001). alpha-SMA-expressing activated PSCs enhanced the invasiveness, proliferation, and colony formation of pancreatic cancer cells. CONCLUSIONS: Quantitative analysis of alpha-SMA mRNA expression using formalin-fixed, paraffin-embedded tissue samples was useful to predict the prognosis of patients with PDAC. Activated PSCs may regulate the malignant behavior of pancreatic cancer cells.
authors.affiliation: From the Departments of *Surgery and Oncology, and daggerAdvanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University; double daggerKyushu University Hospital Cancer Center; and section signDepartment of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Fujita
authors.forename: Kenoki
authors.initials: K
authors.lastname: Ohuchida
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mizumoto
authors.forename: Kohei
authors.initials: K
authors.lastname: Nakata
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kayashima
authors.forename: Lin
authors.initials: L
authors.lastname: Cui
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Manabe
authors.forename: Takao
authors.initials: T
authors.lastname: Ohtsuka
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka