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PDGFRβ expression in tumor stroma of pancreatic adenocarcinoma as a reliable prognostic marker

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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.

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Acknowledgments

We are grateful to Prof. Michael W. Miller (Miller Takemoto & Partners) for help with the manuscript. This research was supported by a Grant-in-Aid for Scientific Research (KAKENHI) and by the Japan Society for the Promotion of Science (JSPS) through the “Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program),” initiated by the Council for Science and Technology Policy (CSTP). The study sponsors had no involvement in the study design, in the collection, analysis, and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Department of Translational Pathology, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan

    Sayaka Yuzawa & Hiroshi Nishihara

  2. Medical Scientist Training Program, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Mitsunobu R. Kano

  3. Division of Gastroenterological and General Surgery, Department of Surgery, Asahikawa Medical College, 1-1 Midori-ga-oka Higashi 2-jo 1-chome, Asahikawa-shi, Hokkaido, 078-8510, Japan

    Takahiro Einama

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  1. Sayaka Yuzawa
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  2. Mitsunobu R. Kano
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  3. Takahiro Einama
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  4. Hiroshi Nishihara
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Correspondence to Mitsunobu R. Kano.

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Yuzawa, S., Kano, M.R., Einama, T. et al. PDGFRβ expression in tumor stroma of pancreatic adenocarcinoma as a reliable prognostic marker. Med Oncol 29, 2824–2830 (2012). https://doi.org/10.1007/s12032-012-0193-0

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  • DOI: https://doi.org/10.1007/s12032-012-0193-0

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