Podoplanin expressing cancer associated fibroblasts are associated with unfavourable prognosis in adenocarcinoma of the
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RESEARCH PAPER
Podoplanin expressing cancer associated fibroblasts are associated with unfavourable prognosis in adenocarcinoma of the esophagus Sebastian F. Schoppmann • Bettina Jesch • Martin F. Riegler Florian Maroske • Katrin Schwameis • Gerd Jomrich • Peter Birner
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Received: 23 May 2012 / Accepted: 6 November 2012 / Published online: 19 November 2012 Ó Springer Science+Business Media Dordrecht 2012
Abstract Overexpression of the mucin-type sialoglycoprotein podoplanin in cancer associated fibroblasts (CAFs) was recently shown to be associated with tumor progression, metastasis and poor prognosis in lung and breast cancer. Here we investigate the role of podoplanin expressing CAFs in esophagal adenocarcinoma (AC), its precursor lesions and metastases. Podoplanin expression was investigated immunohistochemically in 200 formalin-fixed, paraffin embedded specimens of invasive esophagal ACs, their corresponding metastases and 35 precursor lesions. Podoplanin expressing CAFs (CAF?) were observed in 22 % of patients with invasive AC, but not in precursor lesions. CAF? correlated with tumor stage (p = 0.004), lymphovascular tumor invasion (p = 0.018) and lymph node metastasis (p = 0.0016). Patients with CAF? had a significant shorter disease free and overall survival (p \ 0.05, Cox regression). Podoplanin expressing CAFs were only rarely observed in lymph node and distant metastases, as well as in local recurrences of ACs. Podoplanin expression in AC tumor cells was seen in only four cases. In around 20 % of patients with esophagal AC, podoplanin expressing CAFs are evident, defining a high risk subgroup.
S. F. Schoppmann (&) B. Jesch M. F. Riegler F. Maroske K. Schwameis G. Jomrich P. Birner Department of Surgery and Comprehensive Cancer Center Vienna (CCC-GET), Medical University of Vienna-General Hospital, Waehringer Guertel 18-20, 1090 Vienna, Austria e-mail: [email protected] P. Birner Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
In these patients, podoplanin expressing CAFs might represent new therapeutical targets. Keywords Podoplanin Esophagal cancer Cancer associated fibroblasts Prognosis
Introduction Malignant tumors consist of two cell types: a collection of mutated cells growing uncontrolled–the so called tumor cells-and various other co-opted non-malignant cell types including fibroblasts, blood and lymphatic endothelial cells and immune cells [1]. The cytokine mediated tumor-stromal interaction has been shown to play a critical role in tumor progression and metastasis [2–4]. Activated fibroblasts that are recruited into cancer tissue (the so called cancer-associated fibroblasts, CAFs) are supposed to promote tumor progression by secreting different cytokines and growth factors [5, 6]. The mucin-type sialoglycoprotein podoplanin, a selective marker of lymphatic endothelium, was recently shown to be overexpressed in CAFs of adenocarcinomas of the lung and breast cancer where it was associated with tumor progression, metastasis an
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