Martin K Angele1,2, Thomas Knösel3,2, Florian Bösch1,2, Annelore Altendorf-Hofmann4, Vanessa Koliogiannis5,2, Harun Ilhan6,2, Sven Jacob1,2, Elise Pretzsch1,2, Svenja Nölting7,8, Jens Werner1,2, Frederick Klauschen3,2, Christoph J Auernhammer9,10. 1. Department of General, Visceral, and Transplant Surgery, University Hospital, LMU Klinikum, Ludwig-Maximilians-University Munich, Munich, Germany. 2. Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), University Hospital, LMU Klinikum, Ludwig-Maximilians-University of Munich, Munich, Germany. 3. Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany. 4. Department of General, Visceral Und Vascular Surgery, Friedrich-Schiller University, Jena, Germany. 5. Department of Radiology, University Hospital, LMU Munich, Ludwig-Maximilians-University Munich, Munich, Germany. 6. Department of Nuclear Medicine, University Hospital, LMU Klinikum, Ludwig-Maximilians-University Munich, Munich, Germany. 7. Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland. 8. Department of Internal Medicine 4, University Hospital, LMU Klinikum, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377, Munich, Germany. 9. Department of Internal Medicine 4, University Hospital, LMU Klinikum, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377, Munich, Germany. Christoph.Auernhammer@med.uni-muenchen.de. 10. Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), University Hospital, LMU Klinikum, Ludwig-Maximilians-University of Munich, Munich, Germany. Christoph.Auernhammer@med.uni-muenchen.de.
Abstract
INTRODUCTION: Small intestine neuroendocrine neoplasms (siNENs) will attain more importance due to their increasing incidence. Moreover, siNENs might lead to a desmoplastic reaction (DR) of the mesentery causing severe complications and deteriorating prognosis. The expression of fibrosis-related proteins appears to be the key mechanisms for the development of this desmoplastic reaction. Therefore, this study aimed to investigate the association of the desmoplastic mesentery with specific fibrosis-related protein expression levels. MATERIALS AND METHODS: By immunohistochemistry, the protein expression levels of four fibrosis-related markers (APLP2, BNIP3L, CD59, DKK3) were investigated in primary tumors of 128 siNENs. The expression levels were correlated with the presence of a desmoplastic reaction and clinico-pathological parameters. RESULTS: In the primary tumor, APLP2, BNIP3L, CD59 and DKK3 were highly expressed in 29.7% (n = 38), 64.9% (n = 83), 92.2% (n = 118) and 80.5% (n = 103), respectively. There was no significant correlation of a single marker or the complete marker panel to the manifestation of a desmoplastic mesentery. The desmoplastic mesentery was significantly associated with clinical symptoms, such as flushing and diarrhea. However, neither the fibrosis-related marker panel nor single marker expressions were associated with clinical symptoms. DISCUSSION: The expression rates of four fibrosis-related markers in the primary tumor display a distinct pattern. However, the expression patterns are not associated with desmoplastic altered mesenteric lymph node metastases and the expression patterns did not correlate with prognosis. These findings suggest alternative mechanisms being responsible for the desmoplastic reaction.
INTRODUCTION: Small intestine neuroendocrine neoplasms (siNENs) will attain more importance due to their increasing incidence. Moreover, siNENs might lead to a desmoplastic reaction (DR) of the mesentery causing severe complications and deteriorating prognosis. The expression of fibrosis-related proteins appears to be the key mechanisms for the development of this desmoplastic reaction. Therefore, this study aimed to investigate the association of the desmoplastic mesentery with specific fibrosis-related protein expression levels. MATERIALS AND METHODS: By immunohistochemistry, the protein expression levels of four fibrosis-related markers (APLP2, BNIP3L, CD59, DKK3) were investigated in primary tumors of 128 siNENs. The expression levels were correlated with the presence of a desmoplastic reaction and clinico-pathological parameters. RESULTS: In the primary tumor, APLP2, BNIP3L, CD59 and DKK3 were highly expressed in 29.7% (n = 38), 64.9% (n = 83), 92.2% (n = 118) and 80.5% (n = 103), respectively. There was no significant correlation of a single marker or the complete marker panel to the manifestation of a desmoplastic mesentery. The desmoplastic mesentery was significantly associated with clinical symptoms, such as flushing and diarrhea. However, neither the fibrosis-related marker panel nor single marker expressions were associated with clinical symptoms. DISCUSSION: The expression rates of four fibrosis-related markers in the primary tumor display a distinct pattern. However, the expression patterns are not associated with desmoplastic altered mesenteric lymph node metastases and the expression patterns did not correlate with prognosis. These findings suggest alternative mechanisms being responsible for the desmoplastic reaction.
Authors: Sven H Loosen; David Schöler; Mark Luedde; Johannes Eschrich; Tom Luedde; Karel Kostev; Christoph Roderburg Journal: J Cancer Res Clin Oncol Date: 2022-07-22 Impact factor: 4.322