title: PDGFRβ expression in tumor stroma of pancreatic adenocarcinoma as a reliable prognostic marker.
abstract: Pancreatic adenocarcinoma is a lethal disease that often develops a desmoplastic reaction in tumor stroma. In general, desmoplasia is thought to promote tumor growth. However, its molecular pathology and prognostic potential have not been fully investigated. Here, we investigate 26 cases of pancreatic ductal adenocarcinoma and examine the clinicopathological association between survival and expression levels of several molecular markers for stromal cells. These include alpha-smooth muscle actin (SMA) and platelet-derived growth factor (PDGF) receptor β (PDGFRβ). Both are markers of activated fibroblasts or pancreatic stellate cells (PSCs) that play an important role in desmoplasia. The staining patterns of both molecular markers were not uniform, so we categorized them into 3 grades (high, middle, and low) according to intensity. Interestingly, Kaplan-Meier analysis revealed that higher expression of PDGFRβ matched shorter prognosis (p=0.0287, log-rank test) as well as lymphatic invasion and lymph node metastasis, whereas SMA did not (p=0.6122). Our results suggest the prognostic potential of cancer stroma via PDGF-B signaling. Regulation of PDGF-B-associated signaling crosstalk between cancer cells and stroma cells, therefore, may indicate a possible therapeutic target for desmoplastic malignant tumors such as pancreatic adenocarcinoma.
authors.affiliation: Department of Translational Pathology, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Yuzawa
authors.forename: Mitsunobu R
authors.initials: MR
authors.lastname: Kano
authors.forename: Takahiro
authors.initials: T
authors.lastname: Einama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishihara
mesh_terms: D000199:Actins / Q000032:analysis; D000230:Adenocarcinoma / Q000737:chemistry / Q000401:mortality* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000032:analysis*; D015996:Survival Rate
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D015415:Biomarkers; D020797:Receptor, Platelet-Derived Growth Factor beta